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01-11-2010 | Review

Genetic variants affecting incretin sensitivity and incretin secretion

Authors: K. Müssig, H. Staiger, F. Machicao, H.-U. Häring, A. Fritsche

Published in: Diabetologia | Issue 11/2010

Abstract

Recent genome-wide association studies identified several novel risk genes for type 2 diabetes. The majority of these type 2 diabetes risk variants confer impaired pancreatic beta cell function. Though the molecular mechanisms by which common genetic variation within these loci affects beta cell function are not completely understood, risk variants may alter glucose-stimulated insulin secretion, proinsulin conversion, and incretin signals. In humans, the incretin effect is mediated by the secretion and insulinotropic action of two peptide hormones, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. This review article aims to give an overview of the type 2 diabetes risk loci that were found to associate with incretin secretion or incretin action, paying special attention to the potential underlying mechanisms.

Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053CrossRefPubMed

Kahn SE (2003) The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 46:3–19CrossRefPubMed

Lieberman LS (2003) Dietary, evolutionary, and modernizing influences on the prevalence of type 2 diabetes. Annu Rev Nutr 23:345–377CrossRefPubMed

Sladek R, Rocheleau G, Rung J et al (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881–885CrossRefPubMed

Saxena R, Voight BF, Lyssenko V et al (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316:1331–1336CrossRefPubMed

Zeggini E, Weedon MN, Lindgren CM et al (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336–1341CrossRefPubMed

Scott LJ, Mohlke KL, Bonnycastle LL et al (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341–1345CrossRefPubMed

Steinthorsdottir V, Thorleifsson G, Reynisdottir I et al (2007) A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet 39:770–775CrossRefPubMed

Frayling TM, Timpson NJ, Weedon MN et al (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894CrossRefPubMed

10.

Gudmundsson J, Sulem P, Steinthorsdottir V et al (2007) Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat Genet 39:977–983CrossRefPubMed

11.

Sandhu MS, Weedon MN, Fawcett KA et al (2007) Common variants in WFS1 confer risk of type 2 diabetes. Nat Genet 39:951–953CrossRefPubMed

12.

Zeggini E, Scott LJ, Saxena R et al (2008) Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 40:638–645CrossRefPubMed

13.

Unoki H, Takahashi A, Kawaguchi T et al (2008) SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet 40:1098–1102CrossRefPubMed

14.

Yasuda K, Miyake K, Horikawa Y et al (2008) Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet 40:1092–1097CrossRefPubMed

15.

Prokopenko I, Langenberg C, Florez JC et al (2009) Variants in MTNR1B influence fasting glucose levels. Nat Genet 41:77–81CrossRefPubMed

16.

Staiger H, Stancakova A, Zilinskaite J et al (2008) A candidate type 2 diabetes polymorphism near the HHEX locus affects acute glucose-stimulated insulin release in European populations: results from the EUGENE2 study. Diabetes 57:514–517CrossRefPubMed

17.

Staiger H, Machicao F, Stefan N et al (2007) Polymorphisms within novel risk loci for type 2 diabetes determine beta-cell function. PLoS One 2:e832CrossRefPubMed

18.

Moore AF, Jablonski KA, McAteer JB et al (2008) Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program. Diabetes 57:2503–2510CrossRefPubMed

19.

Grarup N, Rose CS, Andersson EA et al (2007) Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10, 705 Danish subjects: validation and extension of genome-wide association studies. Diabetes 56:3105–3111CrossRefPubMed

20.

Pascoe L, Tura A, Patel SK et al (2007) Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function. Diabetes 56:3101–3104CrossRefPubMed

21.

Kirchhoff K, Machicao F, Haupt A et al (2008) Polymorphisms in the TCF7L2, CDKAL1 and SLC30A8 genes are associated with impaired proinsulin conversion. Diabetologia 51:597–601CrossRefPubMed

22.

Rong R, Hanson RL, Ortiz D et al (2009) Association analysis of variation in/near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B with type 2 diabetes and related quantitative traits in Pima Indians. Diabetes 58:478–488CrossRefPubMed

23.

Palmer ND, Goodarzi MO, Langefeld CD et al (2008) Quantitative trait analysis of type 2 diabetes susceptibility loci identified from whole genome association studies in the Insulin Resistance Atherosclerosis Family Study. Diabetes 57:1093–1100CrossRefPubMed

24.

Groenewoud MJ, Dekker JM, Fritsche A et al (2008) Variants of CDKAL1 and IGF2BP2 affect first-phase insulin secretion during hyperglycaemic clamps. Diabetologia 51:1659–1663CrossRefPubMed

25.

Stancakova A, Pihlajamaki J, Kuusisto J et al (2008) Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance. J Clin Endocrinol Metab 93:1924–1930CrossRefPubMed

26.

Pascoe L, Frayling TM, Weedon MN et al (2008) Beta cell glucose sensitivity is decreased by 39% in non-diabetic individuals carrying multiple diabetes-risk alleles compared with those with no risk alleles. Diabetologia 51:1989–1992CrossRefPubMed

27.

Palmer ND, Lehtinen AB, Langefeld CD et al (2008) Association of TCF7L2 gene polymorphisms with reduced acute insulin response in Hispanic Americans. J Clin Endocrinol Metab 93:304–309CrossRefPubMed

28.

Munoz J, Lok KH, Gower BA et al (2006) Polymorphism in the transcription factor 7-like 2 (TCF7L2) gene is associated with reduced insulin secretion in nondiabetic women. Diabetes 55:3630–3634CrossRefPubMed

29.

Saxena R, Gianniny L, Burtt NP et al (2006) Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals. Diabetes 55:2890–2895CrossRefPubMed

30.

Lyssenko V, Nagorny CL, Erdos MR et al (2009) Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat Genet 41:82–88CrossRefPubMed

31.

Staiger H, Machicao F, Kantartzis K et al (2008) Novel meta-analysis-derived type 2 diabetes risk loci do not determine prediabetic phenotypes. PLoS One 3:e3019CrossRefPubMed

32.

Staiger H, Machicao F, Schäfer SA et al (2008) Polymorphisms within the novel type 2 diabetes risk locus MTNR1B determine beta-cell function. PLoS One 3:e3962CrossRefPubMed

33.

Grarup N, Andersen G, Krarup NT et al (2008) Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged Danes. Diabetes 57:2534–2540CrossRefPubMed

34.

Nielsen EM, Hansen L, Carstensen B et al (2003) The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. Diabetes 52:573–577CrossRefPubMed

35.

Sparso T, Andersen G, Albrechtsen A et al (2008) Impact of polymorphisms in WFS1 on prediabetic phenotypes in a population-based sample of middle-aged people with normal and abnormal glucose regulation. Diabetologia 51:1646–1652CrossRefPubMed

36.

Florez JC, Jablonski KA, McAteer J et al (2008) Testing of diabetes-associated WFS1 polymorphisms in the Diabetes Prevention Program. Diabetologia 51:451–457CrossRefPubMed

37.

Wegner L, Hussain MS, Pilgaard K et al (2008) Impact of TCF7L2 rs7903146 on insulin secretion and action in young and elderly Danish twins. J Clin Endocrinol Metab 93:4013–4019CrossRefPubMed

38.

Gonzalez-Sanchez JL, Martinez-Larrad MT, Fernandez-Perez C, Kubaszek A, Laakso M, Serrano-Rios M (2003) K121Q PC-1 gene polymorphism is not associated with insulin resistance in a Spanish population. Obes Res 11:603–605CrossRefPubMed

39.

Loos RJ, Franks PW, Francis RW et al (2007) TCF7L2 polymorphisms modulate proinsulin levels and beta-cell function in a British Europid population. Diabetes 56:1943–1947CrossRefPubMed

40.

Stolerman ES, Manning AK, McAteer JB et al (2009) TCF7L2 variants are associated with increased proinsulin/insulin ratios but not obesity traits in the Framingham Heart Study. Diabetologia 52:614–620CrossRefPubMed

41.

Holst JJ, Vilsboll T, Deacon CF (2009) The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 297:127–136CrossRefPubMed

42.

Meier JJ, Nauck MA (2010) Is the diminished incretin effect in type 2 diabetes just an epi-phenomenon of impaired beta-cell function? Diabetes 59:1117–1125CrossRefPubMed

43.

Jin T (2008) The WNT signalling pathway and diabetes mellitus. Diabetologia 51:1771–1780CrossRefPubMed

44.

Figeac F, Uzan B, Faro M, Chelali N, Portha B, Movassat J (2010) Neonatal growth and regeneration of β cells are regulated by the Wnt/β-catenin signaling in normal and diabetic rats. Am J Physiol Endocrinol Metab 298:E245–E256CrossRefPubMed

45.

Jin T (2008) Mechanisms underlying proglucagon gene expression. J Endocrinol 198:17–28CrossRefPubMed

46.

Liu Z, Habener JF (2008) Glucagon-like peptide-1 activation of TCF7L2-dependent Wnt signaling enhances pancreatic beta cell proliferation. J Biol Chem 283:8723–8735CrossRefPubMed

47.

Bordonaro M (2009) Role of Wnt signaling in the development of type 2 diabetes. Vitam Horm 80:563–581CrossRefPubMed

48.

Loder MK, da Silva XG, McDonald A, Rutter GA (2008) TCF7L2 controls insulin gene expression and insulin secretion in mature pancreatic beta-cells. Biochem Soc Trans 36:357–359CrossRefPubMed

49.

Shu L, Matveyenko AV, Kerr-Conte J, Cho JH, McIntosh CH, Maedler K (2009) Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function. Hum Mol Genet 18:2388–2399CrossRefPubMed

50.

Lyssenko V, Lupi R, Marchetti P et al (2007) Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest 117:2155–2163CrossRefPubMed

51.

Shu L, Sauter NS, Schulthess FT, Matveyenko AV, Oberholzer J, Maedler K (2008) Transcription factor 7-like 2 regulates beta-cell survival and function in human pancreatic islets. Diabetes 57:645–653CrossRefPubMed

52.

da Silva XG, Loder MK, McDonald A et al (2009) TCF7L2 regulates late events in insulin secretion from pancreatic islet beta-cells. Diabetes 58:894–905CrossRef

53.

Grant SF, Thorleifsson G, Reynisdottir I et al (2006) Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 38:320–323CrossRefPubMed

54.

Florez JC, Jablonski KA, Bayley N et al (2006) TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med 355:241–250CrossRefPubMed

55.

Helgason A, Palsson S, Thorleifsson G et al (2007) Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nat Genet 39:218–225CrossRefPubMed

56.

Scott LJ, Bonnycastle LL, Willer CJ et al (2006) Association of transcription factor 7-like 2 (TCF7L2) variants with type 2 diabetes in a Finnish sample. Diabetes 55:2649–2653CrossRefPubMed

57.

Damcott CM, Pollin TI, Reinhart LJ et al (2006) Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish: replication and evidence for a role in both insulin secretion and insulin resistance. Diabetes 55:2654–2659CrossRefPubMed

58.

Schäfer SA, Tschritter O, Machicao F et al (2007) Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Diabetologia 50:2443–2450CrossRefPubMed

59.

Villareal DT, Robertson H, Bell GI et al (2010) TCF7L2 variant rs7903146 affects the risk of type 2 diabetes by modulating incretin action. Diabetes 59:479–485CrossRefPubMed

60.

Pilgaard K, Jensen CB, Schou JH et al (2009) The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. Diabetologia 52:1298–1307CrossRefPubMed

61.

Knauf C, Cani PD, Perrin C et al (2005) Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage. J Clin Invest 115:3554–3563CrossRefPubMed

62.

Saxena R, Hivert MF, Langenberg C et al (2010) Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet 42:142–148CrossRefPubMed

63.

Yaqub T, Tikhonova IG, Lattig J et al (2010) Identification of determinants of glucose-dependent insulinotropic polypeptide receptor that interact with N-terminal biologically active region of the natural ligand. Mol Pharmacol 77:547–558CrossRefPubMed

64.

Gupta D, Peshavaria M, Monga N, Jetton TL, Leahy JL (2010) Physiologic and pharmacologic modulation of GIP receptor expression in ss-cells by PPARgamma signaling: possible mechanism for the GIP resistance in type 2 diabetes. Diabetes 59:1445–1450CrossRefPubMed

65.

Miyawaki K, Yamada Y, Yano H et al (1999) Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice. Proc Natl Acad Sci USA 96:14843–14847CrossRefPubMed

66.

Renner S, Fehlings C, Herbach N et al (2010) Glucose intolerance and reduced proliferation of pancreatic beta-cells in transgenic pigs with impaired glucose-dependent insulinotropic polypeptide function. Diabetes 59:1228–1238CrossRefPubMed

67.

Widenmaier SB, Kim SJ, Yang GK et al (2010) A GIP receptor agonist exhibits beta-cell anti-apoptotic actions in rat models of diabetes resulting in improved beta-cell function and glycemic control. PLoS One 5:e9590CrossRefPubMed

68.

Almind K, Ambye L, Urhammer SA et al (1998) Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell responses and functional expression studies in Chinese hamster fibroblast cells. Diabetologia 41:1194–1198CrossRefPubMed

69.

Kubota A, Yamada Y, Hayami T et al (1996) Identification of two missense mutations in the GIP receptor gene: a functional study and association analysis with NIDDM: no evidence of association with Japanese NIDDM subjects. Diabetes 45:1701–1705CrossRefPubMed

70.

Nitz I, Fisher E, Weikert C et al (2007) Association analyses of GIP and GIPR polymorphisms with traits of the metabolic syndrome. Mol Nutr Food Res 51:1046–1052CrossRefPubMed

71.

Schäfer SA, Müssig K, Staiger H et al (2009) A common genetic variant in WFS1 determines impaired glucagon-like peptide-1-induced insulin secretion. Diabetologia 52:1075–1082CrossRefPubMed

72.

Simonis-Bik AM, Nijpels G, van Haeften TW et al (2010) Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function. Diabetes 59:293–301CrossRefPubMed

73.

Takeda K, Inoue H, Tanizawa Y et al (2001) WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain. Hum Mol Genet 10:477–484CrossRefPubMed

74.

Ishihara H, Takeda S, Tamura A et al (2004) Disruption of the WFS1 gene in mice causes progressive beta-cell loss and impaired stimulus-secretion coupling in insulin secretion. Hum Mol Genet 13:1159–1170CrossRefPubMed

75.

Riggs AC, Bernal-Mizrachi E, Ohsugi M et al (2005) Mice conditionally lacking the Wolfram gene in pancreatic islet beta cells exhibit diabetes as a result of enhanced endoplasmic reticulum stress and apoptosis. Diabetologia 48:2313–2321CrossRefPubMed

76.

Yamada T, Ishihara H, Tamura A et al (2006) WFS1-deficiency increases endoplasmic reticulum stress, impairs cell cycle progression and triggers the apoptotic pathway specifically in pancreatic beta-cells. Hum Mol Genet 15:1600–1609CrossRefPubMed

77.

Xu R, Xia B, Geng J et al (2009) Expression and localization of Wolfram syndrome 1 gene in the developing rat pancreas. World J Gastroenterol 15:5425–5431CrossRefPubMed

78.

Scheuner D, Kaufman RJ (2008) The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetes. Endocr Rev 29:317–333CrossRefPubMed

79.

Fonseca SG, Fukuma M, Lipson KL et al (2005) WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells. J Biol Chem 280:39609–39615CrossRefPubMed

80.

Marciniak SJ, Ron D (2006) Endoplasmic reticulum stress signaling in disease. Physiol Rev 86:1133–1149CrossRefPubMed

81.

Jonsson A, Isomaa B, Tuomi T et al (2009) A variant in the KCNQ1 gene predicts future type 2 diabetes and mediates impaired insulin secretion. Diabetes 58:2409–2413CrossRefPubMed

82.

Müssig K, Staiger H, Machicao F et al (2009) Association of type 2 diabetes candidate polymorphisms in KCNQ1 with incretin and insulin secretion. Diabetes 58:1715–1720CrossRefPubMed

83.

Holmkvist J, Banasik K, Andersen G et al (2009) The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load. PLoS One 4:e5872CrossRefPubMed

84.

Tan JT, Nurbaya S, Gardner D, Ye S, Tai ES, Ng DP (2009) Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore. Diabetes 58:1445–1449CrossRefPubMed

85.

Towbin JA, Vatta M (2001) Molecular biology and the prolonged QT syndromes. Am J Med 110:385–398CrossRefPubMed

86.

Thevenod F (2002) Ion channels in secretory granules of the pancreas and their role in exocytosis and release of secretory proteins. Am J Physiol Cell Physiol 283:C651–C672PubMed

87.

Ullrich S, Su J, Ranta F et al (2005) Effects of I(Ks) channel inhibitors in insulin-secreting INS-1 cells. Pflugers Arch 451:428–436CrossRefPubMed

88.

Vallon V, Grahammer F, Volkl H et al (2005) KCNQ1-dependent transport in renal and gastrointestinal epithelia. Proc Natl Acad Sci USA 102:17864–17869CrossRefPubMed

89.

Dupuis J, Langenberg C, Prokopenko I et al (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 42:105–116CrossRefPubMed

90.

Wolford JK, Yeatts KA, Dhanjal SK et al (2005) Sequence variation in PPARG may underlie differential response to troglitazone. Diabetes 54:3319–3325CrossRefPubMed

91.

Kang ES, Park SY, Kim HJ et al (2005) Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma2 gene on rosiglitazone response in type 2 diabetes. Clin Pharmacol Ther 78:202–208CrossRefPubMed

92.

Blüher M, Lubben G, Paschke R (2003) Analysis of the relationship between the Pro12Ala variant in the PPAR-gamma2 gene and the response rate to therapy with pioglitazone in patients with type 2 diabetes. Diabetes Care 26:825–831CrossRefPubMed

93.

Snitker S, Watanabe RM, Ani I et al (2004) Changes in insulin sensitivity in response to troglitazone do not differ between subjects with and without the common, functional Pro12Ala peroxisome proliferator-activated receptor-gamma2 gene variant: results from the Troglitazone in Prevention of Diabetes (TRIPOD) study. Diabetes Care 27:1365–1368CrossRefPubMed

94.

Florez JC, Jablonski KA, Sun MW et al (2007) Effects of the type 2 diabetes-associated PPARG P12A polymorphism on progression to diabetes and response to troglitazone. J Clin Endocrinol Metab 92:1502–1509CrossRefPubMed

95.

Sesti G, Laratta E, Cardellini M et al (2006) The E23K variant of KCNJ11 encoding the pancreatic beta-cell adenosine 5′-triphosphate-sensitive potassium channel subunit Kir6.2 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes. J Clin Endocrinol Metab 91:2334–2339

96.

Florez JC, Jablonski KA, Kahn SE et al (2007) Type 2 diabetes-associated missense polymorphisms KCNJ11 E23K and ABCC8 A1369S influence progression to diabetes and response to interventions in the Diabetes Prevention Program. Diabetes 56:531–536CrossRefPubMed

97.

Yu M, Xu XJ, Yin JY et al (2010) KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) polymorphisms affect therapeutic efficacy of repaglinide in Chinese patients with type 2 diabetes. Clin Pharmacol Ther 87:330–335CrossRefPubMed

98.

Gloyn AL, Hashim Y, Ashcroft SJ, Ashfield R, Wiltshire S, Turner RC (2001) Association studies of variants in promoter and coding regions of beta-cell ATP-sensitive K-channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS 53). Diabet Med 18:206–212CrossRefPubMed

99.

Kimber CH, Doney AS, Pearson ER et al (2007) TCF7L2 in the Go-DARTS study: evidence for a gene dose effect on both diabetes susceptibility and control of glucose levels. Diabetologia 50:1186–1191CrossRefPubMed

100.

Pearson ER, Donnelly LA, Kimber C et al (2007) Variation in TCF7L2 influences therapeutic response to sulfonylureas: a GoDARTs study. Diabetes 56:2178–2182CrossRefPubMed

Title: Genetic variants affecting incretin sensitivity and incretin secretion
Authors: K. Müssig
H. Staiger
F. Machicao
H.-U. Häring
A. Fritsche
Publication date: 01-11-2010
Publisher: Springer-Verlag
Published in: Diabetologia / Issue 11/2010
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-010-1876-8

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