Skip to main content
Top
Published in: Journal of Translational Medicine 1/2012

Open Access 01-12-2012 | Review

Future detection and monitoring of diabetes may entail analysis of both β-cell function and volume: How markers of β-cell loss may assist

Authors: Anita V Neutzsky-Wulff, Kim V Andreassen, Sara T Hjuler, Michael Feigh, Anne-Christine Bay-Jensen, Qinlong Zheng, Kim Henriksen, Morten A Karsdal

Published in: Journal of Translational Medicine | Issue 1/2012

Login to get access

Abstract

Disease heterogeneity is as major issue in Type II Diabetes Mellitus (T2DM), and this patient inter-variability might not be sufficiently reflected by measurements of glycated haemoglobin (HbA1c).
Β-cell dysfunction and β-cell death are initiating factors in development of T2DM. In fact, β-cells are known vanish prior to the development of T2DM, and autopsy of overt T2DM patients have shown a 60% reduction in β-cell mass.
As the decline in β-cell function and mass have been proven to be pathological traits in T2DM, methods for evaluating β-cell loss is becoming of more interest. However, evaluation of β-cell death or loss is currently invasive and unattainable for the vast majority of diabetes patients. Serological markers, reflecting β-cell loss would be advantageous to detect and monitor progression of T2DM. Biomarkers with such capacities could be neo-epitopes of proteins with high β-cell specificity containing post translational modifications. Such tools may segregate T2DM patients into more appropriate treatment groups, based on their β-cell status, which is currently not possible. Presently individuals presenting with adequately elevated levels of both insulin and glucose are classified as T2DM patients, while an important subdivision of those is pending, namely those patients with sufficient β-cell capacity and those without. This may warrant two very different treatment options and patient care paths.
Serological biomarkers reflecting β-cell health status may also assist development of new drugs for T2DM and aid physicians in better characterization of individual patients and tailor individual treatments and patient care protocols.
Appendix
Available only for authorised users
Literature
1.
go back to reference Gerich JE: The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocr Rev. 1998, 19: 491-503. 10.1210/er.19.4.491.PubMed Gerich JE: The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocr Rev. 1998, 19: 491-503. 10.1210/er.19.4.491.PubMed
2.
go back to reference Hinke SA: Finding GAD: early detection of beta-cell injury. Endocrinology. 2007, 148: 4568-4571. 10.1210/en.2007-0861.PubMed Hinke SA: Finding GAD: early detection of beta-cell injury. Endocrinology. 2007, 148: 4568-4571. 10.1210/en.2007-0861.PubMed
3.
go back to reference Daneman D: Type 1 diabetes. Lancet. 2006, 367: 847-858. 10.1016/S0140-6736(06)68341-4.PubMed Daneman D: Type 1 diabetes. Lancet. 2006, 367: 847-858. 10.1016/S0140-6736(06)68341-4.PubMed
4.
go back to reference Wajchenberg BL: beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev. 2007, 28: 187-218.PubMed Wajchenberg BL: beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev. 2007, 28: 187-218.PubMed
5.
go back to reference Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL: Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes. 2005, 54 (Suppl 2): S97-S107.PubMed Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL: Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes. 2005, 54 (Suppl 2): S97-S107.PubMed
6.
go back to reference Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC: Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003, 52: 102-110. 10.2337/diabetes.52.1.102.PubMed Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC: Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003, 52: 102-110. 10.2337/diabetes.52.1.102.PubMed
7.
go back to reference Meier JJ, Breuer TG, Bonadonna RC, Tannapfel A, Uhl W, Schmidt WE, Schrader H, Menge BA: Pancreatic diabetes manifests when beta cell area declines by approximately 65% in humans. Diabetologia. 2012, 55: 1346-1354. 10.1007/s00125-012-2466-8.PubMed Meier JJ, Breuer TG, Bonadonna RC, Tannapfel A, Uhl W, Schmidt WE, Schrader H, Menge BA: Pancreatic diabetes manifests when beta cell area declines by approximately 65% in humans. Diabetologia. 2012, 55: 1346-1354. 10.1007/s00125-012-2466-8.PubMed
8.
go back to reference Karsdal MA, Delvin E, Christiansen C: Protein fingerprints - Relying on and understanding the information of serological protein measurements. Clin Biochem. 2011, 44: 1278-1279. 10.1016/j.clinbiochem.2011.08.1135.PubMed Karsdal MA, Delvin E, Christiansen C: Protein fingerprints - Relying on and understanding the information of serological protein measurements. Clin Biochem. 2011, 44: 1278-1279. 10.1016/j.clinbiochem.2011.08.1135.PubMed
9.
go back to reference Barascuk N, Veidal SS, Larsen L, Larsen DV, Larsen MR, Wang J, Zheng Q, Xing R, Cao Y, Rasmussen LM: A novel assay for extracellular matrix remodeling associated with liver fibrosis: An enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen. Clin Biochem. 2010, 43: 899-904. 10.1016/j.clinbiochem.2010.03.012.PubMed Barascuk N, Veidal SS, Larsen L, Larsen DV, Larsen MR, Wang J, Zheng Q, Xing R, Cao Y, Rasmussen LM: A novel assay for extracellular matrix remodeling associated with liver fibrosis: An enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen. Clin Biochem. 2010, 43: 899-904. 10.1016/j.clinbiochem.2010.03.012.PubMed
10.
go back to reference Barascuk N, Vassiliadis E, Larsen L, Wang J, Zheng Q, Xing R, Cao Y, Crespo C, Lapret I, Sabatini M: Development and validation of an enzyme-linked immunosorbent assay for the quantification of a specific MMP-9 mediated degradation fragment of type III collagen–A novel biomarker of atherosclerotic plaque remodeling. Clin Biochem. 2011, 44: 900-906. 10.1016/j.clinbiochem.2011.04.004.PubMed Barascuk N, Vassiliadis E, Larsen L, Wang J, Zheng Q, Xing R, Cao Y, Crespo C, Lapret I, Sabatini M: Development and validation of an enzyme-linked immunosorbent assay for the quantification of a specific MMP-9 mediated degradation fragment of type III collagen–A novel biomarker of atherosclerotic plaque remodeling. Clin Biochem. 2011, 44: 900-906. 10.1016/j.clinbiochem.2011.04.004.PubMed
11.
go back to reference Henriksen K, Leeming DJ, Christiansen C, Karsdal MA: Use of bone turnover markers in clinical osteoporosis assessment in women: current issues and future options. Womens Health (Lond Engl). 2011, 7: 689-698. 10.2217/whe.11.74. Henriksen K, Leeming DJ, Christiansen C, Karsdal MA: Use of bone turnover markers in clinical osteoporosis assessment in women: current issues and future options. Womens Health (Lond Engl). 2011, 7: 689-698. 10.2217/whe.11.74.
12.
go back to reference Leeming DJ, Bay-Jensen AC, Vassiliadis E, Larsen MR, Henriksen K, Karsdal MA: Post-translational modifications of the extracellular matrix are key events in cancer progression: opportunities for biochemical marker development. Biomarkers. 2011, 16: 193-205. 10.3109/1354750X.2011.557440.PubMed Leeming DJ, Bay-Jensen AC, Vassiliadis E, Larsen MR, Henriksen K, Karsdal MA: Post-translational modifications of the extracellular matrix are key events in cancer progression: opportunities for biochemical marker development. Biomarkers. 2011, 16: 193-205. 10.3109/1354750X.2011.557440.PubMed
13.
go back to reference Veidal SS, Vassiliadis E, Bay-Jensen AC, Tougas G, Vainer B, Karsdal MA: Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats. Fibrogenesis Tissue Repair. 2010, 3: 5-10.1186/1755-1536-3-5.PubMedPubMedCentral Veidal SS, Vassiliadis E, Bay-Jensen AC, Tougas G, Vainer B, Karsdal MA: Procollagen type I N-terminal propeptide (PINP) is a marker for fibrogenesis in bile duct ligation-induced fibrosis in rats. Fibrogenesis Tissue Repair. 2010, 3: 5-10.1186/1755-1536-3-5.PubMedPubMedCentral
14.
go back to reference Veidal SS, Karsdal MA, Vassiliadis E, Nawrocki A, Larsen MR, Nguyen QH, Hagglund P, Luo Y, Zheng Q, Vainer B: MMP mediated degradation of type VI collagen is highly associated with liver fibrosis–identification and validation of a novel biochemical marker assay. PLoS One. 2011, 6: e24753-10.1371/journal.pone.0024753.PubMedPubMedCentral Veidal SS, Karsdal MA, Vassiliadis E, Nawrocki A, Larsen MR, Nguyen QH, Hagglund P, Luo Y, Zheng Q, Vainer B: MMP mediated degradation of type VI collagen is highly associated with liver fibrosis–identification and validation of a novel biochemical marker assay. PLoS One. 2011, 6: e24753-10.1371/journal.pone.0024753.PubMedPubMedCentral
15.
go back to reference Vassiliadis E, Veidal SS, Simonsen H, Larsen DV, Vainer B, Chen X, Zheng Q, Karsdal MA, Leeming DJ: Immunological detection of the type V collagen propeptide fragment, PVCP-1230, in connective tissue remodeling associated with liver fibrosis. Biomarkers. 2011, 16: 426-433. 10.3109/1354750X.2011.584131.PubMed Vassiliadis E, Veidal SS, Simonsen H, Larsen DV, Vainer B, Chen X, Zheng Q, Karsdal MA, Leeming DJ: Immunological detection of the type V collagen propeptide fragment, PVCP-1230, in connective tissue remodeling associated with liver fibrosis. Biomarkers. 2011, 16: 426-433. 10.3109/1354750X.2011.584131.PubMed
16.
go back to reference Karsdal MA, Henriksen K, Leeming DJ, Mitchell P, Duffin K, Barascuk N, Klickstein L, Aggarwal P, Nemirovskiy O, Byrjalsen I: Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development. Biomarkers. 2009, 14: 181-202. 10.1080/13547500902777608.PubMed Karsdal MA, Henriksen K, Leeming DJ, Mitchell P, Duffin K, Barascuk N, Klickstein L, Aggarwal P, Nemirovskiy O, Byrjalsen I: Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development. Biomarkers. 2009, 14: 181-202. 10.1080/13547500902777608.PubMed
17.
go back to reference Karsdal MA, Henriksen K, Leeming DJ, Woodworth T, Vassiliadis E, Bay-Jensen AC: Novel combinations of Post-Translational Modification (PTM) neo-epitopes provide tissue-specific biochemical markers–are they the cause or the consequence of the disease?. Clin Biochem. 2010, 43: 793-804. 10.1016/j.clinbiochem.2010.03.015.PubMed Karsdal MA, Henriksen K, Leeming DJ, Woodworth T, Vassiliadis E, Bay-Jensen AC: Novel combinations of Post-Translational Modification (PTM) neo-epitopes provide tissue-specific biochemical markers–are they the cause or the consequence of the disease?. Clin Biochem. 2010, 43: 793-804. 10.1016/j.clinbiochem.2010.03.015.PubMed
19.
go back to reference Nolan CJ, Damm P, Prentki M: Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet. 2011, 378: 169-181. 10.1016/S0140-6736(11)60614-4.PubMed Nolan CJ, Damm P, Prentki M: Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet. 2011, 378: 169-181. 10.1016/S0140-6736(11)60614-4.PubMed
20.
go back to reference Gakidou E, Mallinger L, Bbott-Klafter J, Guerrero R, Villalpando S, Ridaura RL, Aekplakorn W, Naghavi M, Lim S, Lozano R: Management of diabetes and associated cardiovascular risk factors in seven countries: a comparison of data from national health examination surveys. Bull World Health Organ. 2011, 89: 172-183. 10.2471/BLT.10.080820.PubMedPubMedCentral Gakidou E, Mallinger L, Bbott-Klafter J, Guerrero R, Villalpando S, Ridaura RL, Aekplakorn W, Naghavi M, Lim S, Lozano R: Management of diabetes and associated cardiovascular risk factors in seven countries: a comparison of data from national health examination surveys. Bull World Health Organ. 2011, 89: 172-183. 10.2471/BLT.10.080820.PubMedPubMedCentral
21.
go back to reference Gromada J, Franklin I, Wollheim CB: Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev. 2007, 28: 84-116.PubMed Gromada J, Franklin I, Wollheim CB: Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev. 2007, 28: 84-116.PubMed
22.
go back to reference Meglasson MD, Matschinsky FM: Pancreatic islet glucose metabolism and regulation of insulin secretion. Diabetes Metab Rev. 1986, 2: 163-214. 10.1002/dmr.5610020301.PubMed Meglasson MD, Matschinsky FM: Pancreatic islet glucose metabolism and regulation of insulin secretion. Diabetes Metab Rev. 1986, 2: 163-214. 10.1002/dmr.5610020301.PubMed
23.
go back to reference In't VP, Marichal M: Microscopic anatomy of the human islet of Langerhans. Adv Exp Med Biol. 2010, 654: 1-19. 10.1007/978-90-481-3271-3_1. In't VP, Marichal M: Microscopic anatomy of the human islet of Langerhans. Adv Exp Med Biol. 2010, 654: 1-19. 10.1007/978-90-481-3271-3_1.
24.
go back to reference Bluestone JA, Herold K, Eisenbarth G: Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature. 2010, 464: 1293-1300. 10.1038/nature08933.PubMed Bluestone JA, Herold K, Eisenbarth G: Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature. 2010, 464: 1293-1300. 10.1038/nature08933.PubMed
25.
go back to reference Cho N, Momose Y: Peroxisome proliferator-activated receptor gamma agonists as insulin sensitizers: from the discovery to recent progress. Curr Top Med Chem. 2008, 8: 1483-1507. 10.2174/156802608786413474.PubMed Cho N, Momose Y: Peroxisome proliferator-activated receptor gamma agonists as insulin sensitizers: from the discovery to recent progress. Curr Top Med Chem. 2008, 8: 1483-1507. 10.2174/156802608786413474.PubMed
26.
go back to reference Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI: Insulin resistance and risk for stroke. Neurology. 2002, 59: 809-815. 10.1212/WNL.59.6.809.PubMed Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI: Insulin resistance and risk for stroke. Neurology. 2002, 59: 809-815. 10.1212/WNL.59.6.809.PubMed
27.
go back to reference Day C: Metabolic syndrome, or What you will: definitions and epidemiology. Diab Vasc Dis Res. 2007, 4: 32-38. 10.3132/dvdr.2007.003.PubMed Day C: Metabolic syndrome, or What you will: definitions and epidemiology. Diab Vasc Dis Res. 2007, 4: 32-38. 10.3132/dvdr.2007.003.PubMed
28.
go back to reference Wild S, Byrne CD: The role of treatment to increase HDL-cholesterol and decrease triglyceride concentrations in prevention of coronary heart disease in Type 2 diabetes. Diabet Med. 2004, 21 (Suppl 4): 8-11.PubMed Wild S, Byrne CD: The role of treatment to increase HDL-cholesterol and decrease triglyceride concentrations in prevention of coronary heart disease in Type 2 diabetes. Diabet Med. 2004, 21 (Suppl 4): 8-11.PubMed
29.
go back to reference American Diabetes A: Standards of medical care in diabetes--2011. Diabetes Care. 2011, 34 (Suppl 1): 11-61. American Diabetes A: Standards of medical care in diabetes--2011. Diabetes Care. 2011, 34 (Suppl 1): 11-61.
30.
go back to reference Krishnamurti U, Steffes MW: Glycohemoglobin: a primary predictor of the development or reversal of complications of diabetes mellitus. Clin Chem. 2001, 47: 1157-1165.PubMed Krishnamurti U, Steffes MW: Glycohemoglobin: a primary predictor of the development or reversal of complications of diabetes mellitus. Clin Chem. 2001, 47: 1157-1165.PubMed
31.
go back to reference Leahy JJ: The mechanisms of action for treatments of type 2 diabetes. Diabetes Educ. 2007, 33 (Suppl 5): 101S-104S.PubMed Leahy JJ: The mechanisms of action for treatments of type 2 diabetes. Diabetes Educ. 2007, 33 (Suppl 5): 101S-104S.PubMed
32.
go back to reference Hansen JB, Arkhammar PO, Bodvarsdottir TB, Wahl P: Inhibition of insulin secretion as a new drug target in the treatment of metabolic disorders. Curr Med Chem. 2004, 11: 1595-1615. 10.2174/0929867043365026.PubMed Hansen JB, Arkhammar PO, Bodvarsdottir TB, Wahl P: Inhibition of insulin secretion as a new drug target in the treatment of metabolic disorders. Curr Med Chem. 2004, 11: 1595-1615. 10.2174/0929867043365026.PubMed
33.
go back to reference Leahy JL: Beta-Cell dysfunction with chronic hyperglycemia: the ''overworked beta-cell'' hypothesis. Biabetes Revs. 1996, 4: 298-319. Leahy JL: Beta-Cell dysfunction with chronic hyperglycemia: the ''overworked beta-cell'' hypothesis. Biabetes Revs. 1996, 4: 298-319.
34.
go back to reference Holman RR: Assessing the potential for alpha-glucosidase inhibitors in prediabetic states. Diabetes Res Clin Pract. 1998, 40 (Suppl): S21-S25.PubMed Holman RR: Assessing the potential for alpha-glucosidase inhibitors in prediabetic states. Diabetes Res Clin Pract. 1998, 40 (Suppl): S21-S25.PubMed
35.
go back to reference Bergman RN: Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes. 1989, 38: 1512-1527. 10.2337/diabetes.38.12.1512.PubMed Bergman RN: Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes. 1989, 38: 1512-1527. 10.2337/diabetes.38.12.1512.PubMed
36.
go back to reference Krentz AJ, Patel MB, Bailey CJ: New drugs for type 2 diabetes mellitus: what is their place in therapy?. Drugs. 2008, 68: 2131-2162. 10.2165/00003495-200868150-00005.PubMed Krentz AJ, Patel MB, Bailey CJ: New drugs for type 2 diabetes mellitus: what is their place in therapy?. Drugs. 2008, 68: 2131-2162. 10.2165/00003495-200868150-00005.PubMed
37.
go back to reference Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC: Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab. 2008, 10 (Suppl 4): 32-42.PubMed Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC: Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab. 2008, 10 (Suppl 4): 32-42.PubMed
38.
go back to reference Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H: Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes. 2003, 52: 581-587. 10.2337/diabetes.52.3.581.PubMed Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H: Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes. 2003, 52: 581-587. 10.2337/diabetes.52.3.581.PubMed
39.
40.
go back to reference Song B, Scheuner D, Ron D, Pennathur S, Kaufman RJ: Chop deletion reduces oxidative stress, improves beta cell function, and promotes cell survival in multiple mouse models of diabetes. J Clin Invest. 2008, 118: 3378-3389. 10.1172/JCI34587.PubMedPubMedCentral Song B, Scheuner D, Ron D, Pennathur S, Kaufman RJ: Chop deletion reduces oxidative stress, improves beta cell function, and promotes cell survival in multiple mouse models of diabetes. J Clin Invest. 2008, 118: 3378-3389. 10.1172/JCI34587.PubMedPubMedCentral
41.
go back to reference Robertson RP, Harmon J, Tran PO, Poitout V: Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes. 2004, 53 (Suppl 1): S119-S124.PubMed Robertson RP, Harmon J, Tran PO, Poitout V: Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes. 2004, 53 (Suppl 1): S119-S124.PubMed
42.
go back to reference Roehrich ME, Mooser V, Lenain V, Herz J, Nimpf J, Azhar S, Bideau M, Capponi A, Nicod P, Haefliger JA: Insulin-secreting beta-cell dysfunction induced by human lipoproteins. J Biol Chem. 2003, 278: 18368-18375. 10.1074/jbc.M300102200.PubMed Roehrich ME, Mooser V, Lenain V, Herz J, Nimpf J, Azhar S, Bideau M, Capponi A, Nicod P, Haefliger JA: Insulin-secreting beta-cell dysfunction induced by human lipoproteins. J Biol Chem. 2003, 278: 18368-18375. 10.1074/jbc.M300102200.PubMed
43.
go back to reference Hayden MR, Tyagi SC, Kerklo MM, Nicolls MR: Type 2 diabetes mellitus as a conformational disease. JOP. 2005, 6: 287-302.PubMed Hayden MR, Tyagi SC, Kerklo MM, Nicolls MR: Type 2 diabetes mellitus as a conformational disease. JOP. 2005, 6: 287-302.PubMed
44.
go back to reference Butler AE, Janson J, Soeller WC, Butler PC: Increased beta-cell apoptosis prevents adaptive increase in beta-cell mass in mouse model of type 2 diabetes: evidence for role of islet amyloid formation rather than direct action of amyloid. Diabetes. 2003, 52: 2304-2314. 10.2337/diabetes.52.9.2304.PubMed Butler AE, Janson J, Soeller WC, Butler PC: Increased beta-cell apoptosis prevents adaptive increase in beta-cell mass in mouse model of type 2 diabetes: evidence for role of islet amyloid formation rather than direct action of amyloid. Diabetes. 2003, 52: 2304-2314. 10.2337/diabetes.52.9.2304.PubMed
45.
go back to reference Janson J, Ashley RH, Harrison D, McIntyre S, Butler PC: The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles. Diabetes. 1999, 48: 491-498. 10.2337/diabetes.48.3.491.PubMed Janson J, Ashley RH, Harrison D, McIntyre S, Butler PC: The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles. Diabetes. 1999, 48: 491-498. 10.2337/diabetes.48.3.491.PubMed
46.
go back to reference Westermark P, Andersson A, Westermark GT: Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Physiol Rev. 2011, 91: 795-826. 10.1152/physrev.00042.2009.PubMed Westermark P, Andersson A, Westermark GT: Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Physiol Rev. 2011, 91: 795-826. 10.1152/physrev.00042.2009.PubMed
47.
go back to reference Lorenzo A, Razzaboni B, Weir GC, Yankner BA: Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus. Nature. 1994, 368: 756-760. 10.1038/368756a0.PubMed Lorenzo A, Razzaboni B, Weir GC, Yankner BA: Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus. Nature. 1994, 368: 756-760. 10.1038/368756a0.PubMed
48.
go back to reference Bauer DC, Hunter DJ, Abramson SB, Attur M, Corr M, Felson D, Heinegard D, Jordan JM, Kepler TB, Lane NE: Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthr Cartil. 2006, 14: 723-727. 10.1016/j.joca.2006.04.001.PubMed Bauer DC, Hunter DJ, Abramson SB, Attur M, Corr M, Felson D, Heinegard D, Jordan JM, Kepler TB, Lane NE: Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthr Cartil. 2006, 14: 723-727. 10.1016/j.joca.2006.04.001.PubMed
49.
go back to reference Veidal SS, Bay-Jensen AC, Tougas G, Karsdal MA, Vainer B: Serum markers of liver fibrosis: combining the BIPED classification and the neo-epitope approach in the development of new biomarkers. Dis Markers. 2010, 28: 15-28.PubMedPubMedCentral Veidal SS, Bay-Jensen AC, Tougas G, Karsdal MA, Vainer B: Serum markers of liver fibrosis: combining the BIPED classification and the neo-epitope approach in the development of new biomarkers. Dis Markers. 2010, 28: 15-28.PubMedPubMedCentral
50.
go back to reference Coons SJ: The FDA's critical path initiative: a brief introduction. Clin Ther. 2009, 31: 2572-2573. 10.1016/j.clinthera.2009.11.035.PubMed Coons SJ: The FDA's critical path initiative: a brief introduction. Clin Ther. 2009, 31: 2572-2573. 10.1016/j.clinthera.2009.11.035.PubMed
52.
go back to reference Biomarkers Definitions Working Group: Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001, 69: 89-95. Biomarkers Definitions Working Group: Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001, 69: 89-95.
53.
go back to reference Wolffenbuttel BH, Gomis R, Squatrito S, Jones NP, Patwardhan RN: Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in Type 2 diabetic patients. Diabet Med. 2000, 17: 40-47. 10.1046/j.1464-5491.2000.00224.x.PubMed Wolffenbuttel BH, Gomis R, Squatrito S, Jones NP, Patwardhan RN: Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in Type 2 diabetic patients. Diabet Med. 2000, 17: 40-47. 10.1046/j.1464-5491.2000.00224.x.PubMed
54.
go back to reference Charbonnel BH, Matthews DR, Schernthaner G, Hanefeld M, Brunetti P: A long-term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized, double-blind, parallel-group comparison trial. Diabet Med. 2005, 22: 399-405.PubMed Charbonnel BH, Matthews DR, Schernthaner G, Hanefeld M, Brunetti P: A long-term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized, double-blind, parallel-group comparison trial. Diabet Med. 2005, 22: 399-405.PubMed
55.
go back to reference Henriksen K, Byrjalsen I, Qvist P, Beck-Nielsen H, Hansen G, Riis BJ, Perrild H, Svendsen OL, Gram J, Karsdal MA: Efficacy and safety of the PPARgamma partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy. Diabetes Metab Res Rev. 2011, 27: 392-401. 10.1002/dmrr.1187.PubMed Henriksen K, Byrjalsen I, Qvist P, Beck-Nielsen H, Hansen G, Riis BJ, Perrild H, Svendsen OL, Gram J, Karsdal MA: Efficacy and safety of the PPARgamma partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy. Diabetes Metab Res Rev. 2011, 27: 392-401. 10.1002/dmrr.1187.PubMed
56.
go back to reference Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, Thomsen AB, Sondergaard RE, Davies M: Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010, 375: 1447-1456. 10.1016/S0140-6736(10)60307-8.PubMed Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, Thomsen AB, Sondergaard RE, Davies M: Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010, 375: 1447-1456. 10.1016/S0140-6736(10)60307-8.PubMed
57.
go back to reference Rhee EJ, Lee WY, Yoon KH, Yoo SJ, Lee IK, Baik SH, Kim YK, Lee MK, Park KS, Park JY: A multicenter, randomized, placebo-controlled, double-blind phase II trial evaluating the optimal dose, efficacy and safety of LC 15–0444 in patients with type 2 diabetes. Diabetes Obes Metab. 2010, 12: 1113-1119. 10.1111/j.1463-1326.2010.01303.x.PubMed Rhee EJ, Lee WY, Yoon KH, Yoo SJ, Lee IK, Baik SH, Kim YK, Lee MK, Park KS, Park JY: A multicenter, randomized, placebo-controlled, double-blind phase II trial evaluating the optimal dose, efficacy and safety of LC 15–0444 in patients with type 2 diabetes. Diabetes Obes Metab. 2010, 12: 1113-1119. 10.1111/j.1463-1326.2010.01303.x.PubMed
58.
go back to reference Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004, 27: 2628-2635. 10.2337/diacare.27.11.2628.PubMed Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD: Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004, 27: 2628-2635. 10.2337/diacare.27.11.2628.PubMed
59.
go back to reference United Kingdom Prospective Diabetes Study Group: United Kingdom Prospective Diabetes Study 24: a 6-year, randomized, controlled trial comparing sulfonylurea, insulin, and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. Ann Intern Med. 1998, 128: 165-175. United Kingdom Prospective Diabetes Study Group: United Kingdom Prospective Diabetes Study 24: a 6-year, randomized, controlled trial comparing sulfonylurea, insulin, and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. Ann Intern Med. 1998, 128: 165-175.
60.
go back to reference American Diabetes A, American Diabetes Association: Standards of medical care in diabetes--2010. Diabetes Care. 2010, 33 (Suppl 1): 11-61. American Diabetes A, American Diabetes Association: Standards of medical care in diabetes--2010. Diabetes Care. 2010, 33 (Suppl 1): 11-61.
61.
go back to reference Jones GR, Barker G, Goodall I, Schneider HG, Shephard MD, Twigg SM: Change of HbA1c reporting to the new SI units. Med J Aust. 2011, 195: 45-46.PubMed Jones GR, Barker G, Goodall I, Schneider HG, Shephard MD, Twigg SM: Change of HbA1c reporting to the new SI units. Med J Aust. 2011, 195: 45-46.PubMed
62.
go back to reference Steiner DF, Park SY, Stoy J, Philipson LH, Bell GI: A brief perspective on insulin production. Diabetes Obes Metab. 2009, 11 (Suppl 4): 189-196.PubMed Steiner DF, Park SY, Stoy J, Philipson LH, Bell GI: A brief perspective on insulin production. Diabetes Obes Metab. 2009, 11 (Suppl 4): 189-196.PubMed
63.
go back to reference Leahy JL, Halban PA, Weir GC: Relative hypersecretion of proinsulin in rat model of NIDDM. Diabetes. 1991, 40: 985-989. 10.2337/diabetes.40.8.985.PubMed Leahy JL, Halban PA, Weir GC: Relative hypersecretion of proinsulin in rat model of NIDDM. Diabetes. 1991, 40: 985-989. 10.2337/diabetes.40.8.985.PubMed
64.
go back to reference Porte D, Kahn SE: Hyperproinsulinemia and amyloid in NIDDM. Clues to etiology of islet beta-cell dysfunction?. Diabetes. 1989, 38: 1333-1336. 10.2337/diabetes.38.11.1333.PubMed Porte D, Kahn SE: Hyperproinsulinemia and amyloid in NIDDM. Clues to etiology of islet beta-cell dysfunction?. Diabetes. 1989, 38: 1333-1336. 10.2337/diabetes.38.11.1333.PubMed
65.
go back to reference Mykkanen L, Zaccaro DJ, Hales CN, Festa A, Haffner SM: The relation of proinsulin and insulin to insulin sensitivity and acute insulin response in subjects with newly diagnosed type II diabetes: the Insulin Resistance Atherosclerosis Study. Diabetologia. 1999, 42: 1060-1066. 10.1007/s001250051271.PubMed Mykkanen L, Zaccaro DJ, Hales CN, Festa A, Haffner SM: The relation of proinsulin and insulin to insulin sensitivity and acute insulin response in subjects with newly diagnosed type II diabetes: the Insulin Resistance Atherosclerosis Study. Diabetologia. 1999, 42: 1060-1066. 10.1007/s001250051271.PubMed
66.
go back to reference Haffner SM, Mykkanen L, Valdez RA, Stern MP, Holloway DL, Monterrosa A, Bowsher RR: Disproportionately increased proinsulin levels are associated with the insulin resistance syndrome. J Clin Endocrinol Metab. 1994, 79: 1806-1810. 10.1210/jc.79.6.1806.PubMed Haffner SM, Mykkanen L, Valdez RA, Stern MP, Holloway DL, Monterrosa A, Bowsher RR: Disproportionately increased proinsulin levels are associated with the insulin resistance syndrome. J Clin Endocrinol Metab. 1994, 79: 1806-1810. 10.1210/jc.79.6.1806.PubMed
67.
go back to reference Marques RG, Fontaine MJ, Rogers J: C-peptide: much more than a byproduct of insulin biosynthesis. Pancreas. 2004, 29: 231-238. 10.1097/00006676-200410000-00009.PubMed Marques RG, Fontaine MJ, Rogers J: C-peptide: much more than a byproduct of insulin biosynthesis. Pancreas. 2004, 29: 231-238. 10.1097/00006676-200410000-00009.PubMed
68.
go back to reference Polonsky KS, Rubenstein AH: C-peptide as a measure of the secretion and hepatic extraction of insulin. Pitfalls and limitations. Diabetes. 1984, 33: 486-494. 10.2337/diabetes.33.5.486.PubMed Polonsky KS, Rubenstein AH: C-peptide as a measure of the secretion and hepatic extraction of insulin. Pitfalls and limitations. Diabetes. 1984, 33: 486-494. 10.2337/diabetes.33.5.486.PubMed
69.
go back to reference Wallace TM, Levy JC, Matthews DR: Use and abuse of HOMA modeling. Diabetes Care. 2004, 27: 1487-1495. 10.2337/diacare.27.6.1487.PubMed Wallace TM, Levy JC, Matthews DR: Use and abuse of HOMA modeling. Diabetes Care. 2004, 27: 1487-1495. 10.2337/diacare.27.6.1487.PubMed
70.
go back to reference Pfutzner A, Kann PH, Pfutzner AH, Kunt T, Larbig M, Weber MM, Forst T: Intact and total proinsulin: new aspects for diagnosis and treatment of type 2 diabetes mellitus and insulin resistance. Clin Lab. 2004, 50: 567-573.PubMed Pfutzner A, Kann PH, Pfutzner AH, Kunt T, Larbig M, Weber MM, Forst T: Intact and total proinsulin: new aspects for diagnosis and treatment of type 2 diabetes mellitus and insulin resistance. Clin Lab. 2004, 50: 567-573.PubMed
71.
go back to reference Pfutzner A, Pfutzner AH, Larbig M, Forst T: Role of intact proinsulin in diagnosis and treatment of type 2 diabetes mellitus. Diabetes Technol Ther. 2004, 6: 405-412. 10.1089/152091504774198124.PubMed Pfutzner A, Pfutzner AH, Larbig M, Forst T: Role of intact proinsulin in diagnosis and treatment of type 2 diabetes mellitus. Diabetes Technol Ther. 2004, 6: 405-412. 10.1089/152091504774198124.PubMed
72.
go back to reference Loopstra-Masters RC, Haffner SM, Lorenzo C, Wagenknecht LE, Hanley AJ: Proinsulin-to-C-peptide ratio versus proinsulin-to-insulin ratio in the prediction of incident diabetes: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetologia. 2011, 54: 3047-3054. 10.1007/s00125-011-2322-2.PubMed Loopstra-Masters RC, Haffner SM, Lorenzo C, Wagenknecht LE, Hanley AJ: Proinsulin-to-C-peptide ratio versus proinsulin-to-insulin ratio in the prediction of incident diabetes: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetologia. 2011, 54: 3047-3054. 10.1007/s00125-011-2322-2.PubMed
73.
go back to reference Hanley AJ, D'Agostino R, Wagenknecht LE, Saad MF, Savage PJ, Bergman R, Haffner SM: Increased proinsulin levels and decreased acute insulin response independently predict the incidence of type 2 diabetes in the insulin resistance atherosclerosis study. Diabetes. 2002, 51: 1263-1270. 10.2337/diabetes.51.4.1263.PubMed Hanley AJ, D'Agostino R, Wagenknecht LE, Saad MF, Savage PJ, Bergman R, Haffner SM: Increased proinsulin levels and decreased acute insulin response independently predict the incidence of type 2 diabetes in the insulin resistance atherosclerosis study. Diabetes. 2002, 51: 1263-1270. 10.2337/diabetes.51.4.1263.PubMed
74.
go back to reference Goldfine AB, Gerwien RW, Kolberg JA, O'Shea S, Hamren S, Hein GP, Xu XM, Patti ME: Biomarkers in fasting serum to estimate glucose tolerance, insulin sensitivity, and insulin secretion. Clin Chem. 2011, 57: 326-337. 10.1373/clinchem.2010.156133.PubMedPubMedCentral Goldfine AB, Gerwien RW, Kolberg JA, O'Shea S, Hamren S, Hein GP, Xu XM, Patti ME: Biomarkers in fasting serum to estimate glucose tolerance, insulin sensitivity, and insulin secretion. Clin Chem. 2011, 57: 326-337. 10.1373/clinchem.2010.156133.PubMedPubMedCentral
75.
go back to reference Kolberg JA, Jorgensen T, Gerwien RW, Hamren S, McKenna MP, Moler E, Rowe MW, Urdea MS, Xu XM, Hansen T: Development of a type 2 diabetes risk model from a panel of serum biomarkers from the Inter99 cohort. Diabetes Care. 2009, 32: 1207-1212. 10.2337/dc08-1935.PubMedPubMedCentral Kolberg JA, Jorgensen T, Gerwien RW, Hamren S, McKenna MP, Moler E, Rowe MW, Urdea MS, Xu XM, Hansen T: Development of a type 2 diabetes risk model from a panel of serum biomarkers from the Inter99 cohort. Diabetes Care. 2009, 32: 1207-1212. 10.2337/dc08-1935.PubMedPubMedCentral
76.
go back to reference Salomaa V, Havulinna A, Saarela O, Zeller T, Jousilahti P, Jula A, Muenzel T, Aromaa A, Evans A, Kuulasmaa K: Thirty-one novel biomarkers as predictors for clinically incident diabetes. PLoS One. 2010, 5: e10100-10.1371/journal.pone.0010100.PubMedPubMedCentral Salomaa V, Havulinna A, Saarela O, Zeller T, Jousilahti P, Jula A, Muenzel T, Aromaa A, Evans A, Kuulasmaa K: Thirty-one novel biomarkers as predictors for clinically incident diabetes. PLoS One. 2010, 5: e10100-10.1371/journal.pone.0010100.PubMedPubMedCentral
77.
go back to reference Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C: Metabolite profiles and the risk of developing diabetes. Nat Med. 2011, 17: 448-453. 10.1038/nm.2307.PubMedPubMedCentral Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C: Metabolite profiles and the risk of developing diabetes. Nat Med. 2011, 17: 448-453. 10.1038/nm.2307.PubMedPubMedCentral
78.
go back to reference El-Mesallamy HO, El-Derany MO, Hamdy NM: Serum omentin-1 and chemerin levels are interrelated in patients with Type 2 diabetes mellitus with or without ischaemic heart disease. Diabet Med. 2011, 28: 1194-1200. 10.1111/j.1464-5491.2011.03353.x.PubMed El-Mesallamy HO, El-Derany MO, Hamdy NM: Serum omentin-1 and chemerin levels are interrelated in patients with Type 2 diabetes mellitus with or without ischaemic heart disease. Diabet Med. 2011, 28: 1194-1200. 10.1111/j.1464-5491.2011.03353.x.PubMed
79.
go back to reference Leeming DJ, Henriksen K, Byrjalsen I, Qvist P, Madsen SH, Garnero P, Karsdal MA: Is bone quality associated with collagen age?. Osteoporos Int. 2009, 20: 1461-1470. 10.1007/s00198-009-0904-3.PubMed Leeming DJ, Henriksen K, Byrjalsen I, Qvist P, Madsen SH, Garnero P, Karsdal MA: Is bone quality associated with collagen age?. Osteoporos Int. 2009, 20: 1461-1470. 10.1007/s00198-009-0904-3.PubMed
80.
go back to reference Neutzsky-Wulff AV, Sorensen MG, Kocijancic D, Leeming DJ, Dziegiel MH, Karsdal MA, Henriksen K: Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption–implications for osteoclast quality. BMC Musculoskelet Disord. 2010, 11: 109-10.1186/1471-2474-11-109.PubMedPubMedCentral Neutzsky-Wulff AV, Sorensen MG, Kocijancic D, Leeming DJ, Dziegiel MH, Karsdal MA, Henriksen K: Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption–implications for osteoclast quality. BMC Musculoskelet Disord. 2010, 11: 109-10.1186/1471-2474-11-109.PubMedPubMedCentral
81.
go back to reference Teitelbaum SL: Bone resorption by osteoclasts. Science. 2000, 289: 1504-1508. 10.1126/science.289.5484.1504.PubMed Teitelbaum SL: Bone resorption by osteoclasts. Science. 2000, 289: 1504-1508. 10.1126/science.289.5484.1504.PubMed
82.
go back to reference Henriksen K, Leeming DJ, Byrjalsen I, Nielsen RH, Sorensen MG, Dziegiel MH, Martin TJ, Christiansen C, Qvist P, Karsdal MA: Osteoclasts prefer aged bone. Osteoporos Int. 2007, 18: 751-759. 10.1007/s00198-006-0298-4.PubMed Henriksen K, Leeming DJ, Byrjalsen I, Nielsen RH, Sorensen MG, Dziegiel MH, Martin TJ, Christiansen C, Qvist P, Karsdal MA: Osteoclasts prefer aged bone. Osteoporos Int. 2007, 18: 751-759. 10.1007/s00198-006-0298-4.PubMed
83.
go back to reference Bonde M, Qvist P, Fledelius C, Riis BJ, Christiansen C: Immunoassay for quantifying type I collagen degradation products in urine evaluated. Clin Chem. 1994, 40: 2022-2025.PubMed Bonde M, Qvist P, Fledelius C, Riis BJ, Christiansen C: Immunoassay for quantifying type I collagen degradation products in urine evaluated. Clin Chem. 1994, 40: 2022-2025.PubMed
84.
go back to reference Garnero P, Ferreras M, Karsdal MA, Nicamhlaoibh R, Risteli J, Borel O, Qvist P, Delmas PD, Foged NT, Delaisse JM: The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation. J Bone Miner Res. 2003, 18: 859-867. 10.1359/jbmr.2003.18.5.859.PubMed Garnero P, Ferreras M, Karsdal MA, Nicamhlaoibh R, Risteli J, Borel O, Qvist P, Delmas PD, Foged NT, Delaisse JM: The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation. J Bone Miner Res. 2003, 18: 859-867. 10.1359/jbmr.2003.18.5.859.PubMed
85.
go back to reference Bonde M, Qvist P, Fledelius C, Riis BJ, Christiansen C: Applications of an enzyme immunoassay for a new marker of bone resorption (CrossLaps): follow-up on hormone replacement therapy and osteoporosis risk assessment. J Clin Endocrinol Metab. 1995, 80: 864-868. 10.1210/jc.80.3.864.PubMed Bonde M, Qvist P, Fledelius C, Riis BJ, Christiansen C: Applications of an enzyme immunoassay for a new marker of bone resorption (CrossLaps): follow-up on hormone replacement therapy and osteoporosis risk assessment. J Clin Endocrinol Metab. 1995, 80: 864-868. 10.1210/jc.80.3.864.PubMed
86.
go back to reference Zinman B, Haffner SM, Herman WH, Holman RR, Lachin JM, Kravitz BG, Paul G, Jones NP, Aftring RP, Viberti G: Effect of rosiglitazone, metformin, and glyburide on bone biomarkers in patients with type 2 diabetes. J Clin Endocrinol Metab. 2010, 95: 134-142. 10.1210/jc.2009-0572.PubMed Zinman B, Haffner SM, Herman WH, Holman RR, Lachin JM, Kravitz BG, Paul G, Jones NP, Aftring RP, Viberti G: Effect of rosiglitazone, metformin, and glyburide on bone biomarkers in patients with type 2 diabetes. J Clin Endocrinol Metab. 2010, 95: 134-142. 10.1210/jc.2009-0572.PubMed
87.
go back to reference Newby AC: Matrix metalloproteinase inhibition therapy for vascular diseases. Vascul Pharmacol. 2012, 56: 232-244. 10.1016/j.vph.2012.01.007.PubMed Newby AC: Matrix metalloproteinase inhibition therapy for vascular diseases. Vascul Pharmacol. 2012, 56: 232-244. 10.1016/j.vph.2012.01.007.PubMed
88.
go back to reference Tomita T: Immunocytochemical localisation of caspase-3 in pancreatic islets from type 2 diabetic subjects. Pathology. 2010, 42: 432-437. 10.3109/00313025.2010.493863.PubMed Tomita T: Immunocytochemical localisation of caspase-3 in pancreatic islets from type 2 diabetic subjects. Pathology. 2010, 42: 432-437. 10.3109/00313025.2010.493863.PubMed
89.
go back to reference Mueller-Steiner S, Zhou Y, Arai H, Roberson ED, Sun B, Chen J, Wang X, Yu G, Esposito L, Mucke L: Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease. Neuron. 2006, 51: 703-714. 10.1016/j.neuron.2006.07.027.PubMed Mueller-Steiner S, Zhou Y, Arai H, Roberson ED, Sun B, Chen J, Wang X, Yu G, Esposito L, Mucke L: Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease. Neuron. 2006, 51: 703-714. 10.1016/j.neuron.2006.07.027.PubMed
90.
go back to reference Stutzer I, Esterhazy D, Stoffel M: The pancreatic beta cell surface proteome. Diabetologia. 2012, 55: 1877-1889. 10.1007/s00125-012-2531-3.PubMedPubMedCentral Stutzer I, Esterhazy D, Stoffel M: The pancreatic beta cell surface proteome. Diabetologia. 2012, 55: 1877-1889. 10.1007/s00125-012-2531-3.PubMedPubMedCentral
91.
go back to reference Duckworth WC, Bennett RG, Hamel FG: Insulin degradation: progress and potential. Endocr Rev. 1998, 19: 608-624. 10.1210/er.19.5.608.PubMed Duckworth WC, Bennett RG, Hamel FG: Insulin degradation: progress and potential. Endocr Rev. 1998, 19: 608-624. 10.1210/er.19.5.608.PubMed
92.
go back to reference Suckow AT, Comoletti D, Waldrop MA, Mosedale M, Egodage S, Taylor P, Chessler SD: Expression of neurexin, neuroligin, and their cytoplasmic binding partners in the pancreatic beta-cells and the involvement of neuroligin in insulin secretion. Endocrinology. 2008, 149: 6006-6017. 10.1210/en.2008-0274.PubMedPubMedCentral Suckow AT, Comoletti D, Waldrop MA, Mosedale M, Egodage S, Taylor P, Chessler SD: Expression of neurexin, neuroligin, and their cytoplasmic binding partners in the pancreatic beta-cells and the involvement of neuroligin in insulin secretion. Endocrinology. 2008, 149: 6006-6017. 10.1210/en.2008-0274.PubMedPubMedCentral
93.
go back to reference Fujita Y, Wideman RD, Asadi A, Yang GK, Baker R, Webber T, Zhang T, Wang R, Ao Z, Warnock GL: Glucose-dependent insulinotropic polypeptide is expressed in pancreatic islet alpha-cells and promotes insulin secretion. Gastroenterology. 2010, 138: 1966-1975. 10.1053/j.gastro.2010.01.049.PubMed Fujita Y, Wideman RD, Asadi A, Yang GK, Baker R, Webber T, Zhang T, Wang R, Ao Z, Warnock GL: Glucose-dependent insulinotropic polypeptide is expressed in pancreatic islet alpha-cells and promotes insulin secretion. Gastroenterology. 2010, 138: 1966-1975. 10.1053/j.gastro.2010.01.049.PubMed
94.
go back to reference Holst JJ, Deacon CF, Vilsboll T, Krarup T, Madsbad S: Glucagon-like peptide-1, glucose homeostasis and diabetes. Trends Mol Med. 2008, 14: 161-168. 10.1016/j.molmed.2008.01.003.PubMed Holst JJ, Deacon CF, Vilsboll T, Krarup T, Madsbad S: Glucagon-like peptide-1, glucose homeostasis and diabetes. Trends Mol Med. 2008, 14: 161-168. 10.1016/j.molmed.2008.01.003.PubMed
95.
go back to reference Schelshorn D, Joly F, Mutel S, Hampe C, Breton B, Mutel V, Lutjens R: Lateral allosterism in the glucagon receptor family: glucagon-like Peptide 1 induces g-protein-coupled receptor heteromer formation. Mol Pharmacol. 2012, 81: 309-318. 10.1124/mol.111.074757.PubMed Schelshorn D, Joly F, Mutel S, Hampe C, Breton B, Mutel V, Lutjens R: Lateral allosterism in the glucagon receptor family: glucagon-like Peptide 1 induces g-protein-coupled receptor heteromer formation. Mol Pharmacol. 2012, 81: 309-318. 10.1124/mol.111.074757.PubMed
96.
go back to reference Yamada Y, Seino Y: Physiology of GIP–a lesson from GIP receptor knockout mice. Horm Metab Res. 2004, 36: 771-774. 10.1055/s-2004-826162.PubMed Yamada Y, Seino Y: Physiology of GIP–a lesson from GIP receptor knockout mice. Horm Metab Res. 2004, 36: 771-774. 10.1055/s-2004-826162.PubMed
97.
go back to reference Xu G, Kaneto H, Laybutt DR, Duvivier-Kali VF, Trivedi N, Suzuma K, King GL, Weir GC, Bonner-Weir S: Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes. Diabetes. 2007, 56: 1551-1558. 10.2337/db06-1033.PubMed Xu G, Kaneto H, Laybutt DR, Duvivier-Kali VF, Trivedi N, Suzuma K, King GL, Weir GC, Bonner-Weir S: Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes. Diabetes. 2007, 56: 1551-1558. 10.2337/db06-1033.PubMed
98.
go back to reference Vaziri-Sani F, Delli AJ, Elding-Larsson H, Lindblad B, Carlsson A, Forsander G, Ivarsson SA, Ludvigsson J, Marcus C, Lernmark A: A novel triple mix radiobinding assay for the three ZnT8 (ZnT8-RWQ) autoantibody variants in children with newly diagnosed diabetes. J Immunol Methods. 2011, 371: 25-37. 10.1016/j.jim.2011.06.011.PubMedPubMedCentral Vaziri-Sani F, Delli AJ, Elding-Larsson H, Lindblad B, Carlsson A, Forsander G, Ivarsson SA, Ludvigsson J, Marcus C, Lernmark A: A novel triple mix radiobinding assay for the three ZnT8 (ZnT8-RWQ) autoantibody variants in children with newly diagnosed diabetes. J Immunol Methods. 2011, 371: 25-37. 10.1016/j.jim.2011.06.011.PubMedPubMedCentral
99.
go back to reference Reijonen H, Daniels TL, Lernmark A, Nepom GT: GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65. Diabetes. 2000, 49: 1621-1626. 10.2337/diabetes.49.10.1621.PubMed Reijonen H, Daniels TL, Lernmark A, Nepom GT: GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65. Diabetes. 2000, 49: 1621-1626. 10.2337/diabetes.49.10.1621.PubMed
100.
go back to reference Hoppu S, Harkonen T, Ronkainen MS, Simell S, Hekkala A, Toivonen A, Ilonen J, Simell O, Knip M: IA-2 antibody isotypes and epitope specificity during the prediabetic process in children with HLA-conferred susceptibility to type I diabetes. Clin Exp Immunol. 2006, 144: 59-66. 10.1111/j.1365-2249.2006.03033.x.PubMedPubMedCentral Hoppu S, Harkonen T, Ronkainen MS, Simell S, Hekkala A, Toivonen A, Ilonen J, Simell O, Knip M: IA-2 antibody isotypes and epitope specificity during the prediabetic process in children with HLA-conferred susceptibility to type I diabetes. Clin Exp Immunol. 2006, 144: 59-66. 10.1111/j.1365-2249.2006.03033.x.PubMedPubMedCentral
101.
go back to reference Hawa MI, Fava D, Medici F, Deng YJ, Notkins AL, De MG, Leslie RD: Antibodies to IA-2 and GAD65 in type 1 and type 2 diabetes: isotype restriction and polyclonality. Diabetes Care. 2000, 23: 228-233. 10.2337/diacare.23.2.228.PubMed Hawa MI, Fava D, Medici F, Deng YJ, Notkins AL, De MG, Leslie RD: Antibodies to IA-2 and GAD65 in type 1 and type 2 diabetes: isotype restriction and polyclonality. Diabetes Care. 2000, 23: 228-233. 10.2337/diacare.23.2.228.PubMed
102.
go back to reference Waldrop MA, Suckow AT, Marcovina SM, Chessler SD: Release of glutamate decarboxylase-65 into the circulation by injured pancreatic islet beta-cells. Endocrinology. 2007, 148: 4572-4578. 10.1210/en.2006-1367.PubMed Waldrop MA, Suckow AT, Marcovina SM, Chessler SD: Release of glutamate decarboxylase-65 into the circulation by injured pancreatic islet beta-cells. Endocrinology. 2007, 148: 4572-4578. 10.1210/en.2006-1367.PubMed
103.
go back to reference Kukor Z, Mayerle J, Kruger B, Toth M, Steed PM, Halangk W, Lerch MM, Sahin-Toth M: Presence of cathepsin B in the human pancreatic secretory pathway and its role in trypsinogen activation during hereditary pancreatitis. J Biol Chem. 2002, 277: 21389-21396. 10.1074/jbc.M200878200.PubMed Kukor Z, Mayerle J, Kruger B, Toth M, Steed PM, Halangk W, Lerch MM, Sahin-Toth M: Presence of cathepsin B in the human pancreatic secretory pathway and its role in trypsinogen activation during hereditary pancreatitis. J Biol Chem. 2002, 277: 21389-21396. 10.1074/jbc.M200878200.PubMed
104.
go back to reference Lerch MM, Halangk W: Human pancreatitis and the role of cathepsin B. Gut. 2006, 55: 1228-1230. 10.1136/gut.2006.092114.PubMedPubMedCentral Lerch MM, Halangk W: Human pancreatitis and the role of cathepsin B. Gut. 2006, 55: 1228-1230. 10.1136/gut.2006.092114.PubMedPubMedCentral
105.
go back to reference Moore CX, Cooper GJ: Co-secretion of amylin and insulin from cultured islet beta-cells: modulation by nutrient secretagogues, islet hormones and hypoglycemic agents. Biochem Biophys Res Commun. 1991, 179: 1-9. 10.1016/0006-291X(91)91325-7.PubMed Moore CX, Cooper GJ: Co-secretion of amylin and insulin from cultured islet beta-cells: modulation by nutrient secretagogues, islet hormones and hypoglycemic agents. Biochem Biophys Res Commun. 1991, 179: 1-9. 10.1016/0006-291X(91)91325-7.PubMed
106.
go back to reference Bennett RG, Duckworth WC, Hamel FG: Degradation of amylin by insulin-degrading enzyme. J Biol Chem. 2000, 275: 36621-36625. 10.1074/jbc.M006170200.PubMed Bennett RG, Duckworth WC, Hamel FG: Degradation of amylin by insulin-degrading enzyme. J Biol Chem. 2000, 275: 36621-36625. 10.1074/jbc.M006170200.PubMed
107.
go back to reference Yang H, Wright JR: Human beta cells are exceedingly resistant to streptozotocin in vivo. Endocrinology. 2002, 143: 2491-2495. 10.1210/en.143.7.2491.PubMed Yang H, Wright JR: Human beta cells are exceedingly resistant to streptozotocin in vivo. Endocrinology. 2002, 143: 2491-2495. 10.1210/en.143.7.2491.PubMed
108.
go back to reference Burgoyne RD, Morgan A: Secretory granule exocytosis. Physiol Rev. 2003, 83: 581-632.PubMed Burgoyne RD, Morgan A: Secretory granule exocytosis. Physiol Rev. 2003, 83: 581-632.PubMed
109.
go back to reference Maffei A, Liu Z, Witkowski P, Moschella F, Del PG, Liu E, Herold K, Winchester RJ, Hardy MA, Harris PE: Identification of tissue-restricted transcripts in human islets. Endocrinology. 2004, 145: 4513-4521. 10.1210/en.2004-0691.PubMed Maffei A, Liu Z, Witkowski P, Moschella F, Del PG, Liu E, Herold K, Winchester RJ, Hardy MA, Harris PE: Identification of tissue-restricted transcripts in human islets. Endocrinology. 2004, 145: 4513-4521. 10.1210/en.2004-0691.PubMed
110.
go back to reference Mosedale M, Egodage S, Calma RC, Chi NW, Chessler SD: Neurexin-1alpha contributes to insulin-containing secretory granule docking. J Biol Chem. 2012, 287: 6350-6361. 10.1074/jbc.M111.299081.PubMedPubMedCentral Mosedale M, Egodage S, Calma RC, Chi NW, Chessler SD: Neurexin-1alpha contributes to insulin-containing secretory granule docking. J Biol Chem. 2012, 287: 6350-6361. 10.1074/jbc.M111.299081.PubMedPubMedCentral
111.
go back to reference Suckow AT, Zhang C, Egodage S, Comoletti D, Taylor P, Miller MT, Sweet IR, Chessler SD: Transcellular neuroligin-2 interactions enhance insulin secretion and are integral to pancreatic beta cell function. J Biol Chem. 2012, 287: 19816-19826. 10.1074/jbc.M111.280537.PubMedPubMedCentral Suckow AT, Zhang C, Egodage S, Comoletti D, Taylor P, Miller MT, Sweet IR, Chessler SD: Transcellular neuroligin-2 interactions enhance insulin secretion and are integral to pancreatic beta cell function. J Biol Chem. 2012, 287: 19816-19826. 10.1074/jbc.M111.280537.PubMedPubMedCentral
Metadata
Title
Future detection and monitoring of diabetes may entail analysis of both β-cell function and volume: How markers of β-cell loss may assist
Authors
Anita V Neutzsky-Wulff
Kim V Andreassen
Sara T Hjuler
Michael Feigh
Anne-Christine Bay-Jensen
Qinlong Zheng
Kim Henriksen
Morten A Karsdal
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-10-214

Other articles of this Issue 1/2012

Journal of Translational Medicine 1/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.