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Published in: Endocrine 2/2013

01-10-2013 | Review

Beta cell dynamics: beta cell replenishment, beta cell compensation and diabetes

Author: Marlon E. Cerf

Published in: Endocrine | Issue 2/2013

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Abstract

Type 2 diabetes, characterized by persistent hyperglycemia, arises mostly from beta cell dysfunction and insulin resistance and remains a highly complex metabolic disease due to various stages in its pathogenesis. Glucose homeostasis is primarily regulated by insulin secretion from the beta cells in response to prevailing glycemia. Beta cell populations are dynamic as they respond to fluctuating insulin demand. Beta cell replenishment and death primarily regulate beta cell populations. Beta cells, pancreatic cells, and extra-pancreatic cells represent the three tiers for replenishing beta cells. In rodents, beta cell self-replenishment appears to be the dominant source for new beta cells supported by pancreatic cells (non-beta islet cells, acinar cells, and duct cells) and extra-pancreatic cells (liver, neural, and stem/progenitor cells). In humans, beta cell neogenesis from non-beta cells appears to be the dominant source of beta cell replenishment as limited beta cell self-replenishment occurs particularly in adulthood. Metabolic states of increased insulin demand trigger increased insulin synthesis and secretion from beta cells. Beta cells, therefore, adapt to support their physiology. Maintaining physiological beta cell populations is a strategy for targeting metabolic states of persistently increased insulin demand as in diabetes.
Literature
1.
go back to reference K. Sekine, H. Taniguchi, Basics and applications of stem cells in the pancreas. J. Hepatobiliary Pancreat. Sci. 19(6), 594–599 (2012)PubMedCrossRef K. Sekine, H. Taniguchi, Basics and applications of stem cells in the pancreas. J. Hepatobiliary Pancreat. Sci. 19(6), 594–599 (2012)PubMedCrossRef
2.
go back to reference O. Cabrera, M.C. Jacques-Silva, D.M. Berman, A. Fachado, F. Echeverri, R. Poo, A. Khan, N.S. Kenyon, C. Ricordi, P.O. Berggren, A. Caicedo, Automated, high-throughput assays for evaluation of human pancreatic islet function. Cell Transpl. 16(10), 1039–1048 (2008)CrossRef O. Cabrera, M.C. Jacques-Silva, D.M. Berman, A. Fachado, F. Echeverri, R. Poo, A. Khan, N.S. Kenyon, C. Ricordi, P.O. Berggren, A. Caicedo, Automated, high-throughput assays for evaluation of human pancreatic islet function. Cell Transpl. 16(10), 1039–1048 (2008)CrossRef
3.
go back to reference H. Ichii, L. Inverardi, A. Pileggi, R.D. Molano, O. Cabrera, A. Caicedo, S. Messinger, Y. Kuroda, P.O. Berggren, C. Ricordi, A novel method for the assessment of cellular composition and beta-cell viability in human islet preparations. Am. J. Transpl. 5(7), 1635–1645 (2005)CrossRef H. Ichii, L. Inverardi, A. Pileggi, R.D. Molano, O. Cabrera, A. Caicedo, S. Messinger, Y. Kuroda, P.O. Berggren, C. Ricordi, A novel method for the assessment of cellular composition and beta-cell viability in human islet preparations. Am. J. Transpl. 5(7), 1635–1645 (2005)CrossRef
4.
go back to reference M. Brissova, M.J. Fowler, W.E. Nicholson, A. Chu, B. Hirshberg, D.M. Harlan, A.C. Powers, Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy. J. Histochem. Cytochem. 53(9), 1087–1097 (2005)PubMedCrossRef M. Brissova, M.J. Fowler, W.E. Nicholson, A. Chu, B. Hirshberg, D.M. Harlan, A.C. Powers, Assessment of human pancreatic islet architecture and composition by laser scanning confocal microscopy. J. Histochem. Cytochem. 53(9), 1087–1097 (2005)PubMedCrossRef
5.
go back to reference C.N. Street, J.R. Lakey, A.M. Shapiro, S. Imes, R.V. Rajotte, E.A. Ryan, J.G. Lyon, T. Kin, J. Avila, T. Tsujimura, G.S. Korbutt, Islet graft assessment in the Edmonton Protocol: implications for predicting long-term clinical outcome. Diabetes 53(12), 3107–3114 (2004)PubMedCrossRef C.N. Street, J.R. Lakey, A.M. Shapiro, S. Imes, R.V. Rajotte, E.A. Ryan, J.G. Lyon, T. Kin, J. Avila, T. Tsujimura, G.S. Korbutt, Islet graft assessment in the Edmonton Protocol: implications for predicting long-term clinical outcome. Diabetes 53(12), 3107–3114 (2004)PubMedCrossRef
6.
go back to reference I. Todorov, I. Nair, A. Avakian-Mansoorian, J. Rawson, K. Omori, T. Ito, L. Valiente, I. Iglesias-Meza, C. Orr, K.D. Shiang, K. Ferreri, I.H. Al-Abdullah, Y. Mullen, F. Kandeel, Quantitative assessment of beta-cell apoptosis and cell composition of isolated, undisrupted human islets by laser scanning cytometry. Transplantation 90(8), 836–842 (2010)PubMedCrossRef I. Todorov, I. Nair, A. Avakian-Mansoorian, J. Rawson, K. Omori, T. Ito, L. Valiente, I. Iglesias-Meza, C. Orr, K.D. Shiang, K. Ferreri, I.H. Al-Abdullah, Y. Mullen, F. Kandeel, Quantitative assessment of beta-cell apoptosis and cell composition of isolated, undisrupted human islets by laser scanning cytometry. Transplantation 90(8), 836–842 (2010)PubMedCrossRef
7.
go back to reference Weir,G.C., Bonner-Weir, S: Islet beta cell mass in diabetes and how it relates to function, birth, and death. Ann. N. Y. Acad. Sci. (2013). doi:10.1111/nyas.12031 Weir,G.C., Bonner-Weir, S: Islet beta cell mass in diabetes and how it relates to function, birth, and death. Ann. N. Y. Acad. Sci. (2013). doi:10.​1111/​nyas.​12031
8.
go back to reference E. Tarabra, S. Pelengaris, M. Khan, A simple matter of life and death-the trials of postnatal beta-cell mass regulation. Int. J. Endocrinol. 2012, 516718 (2012)PubMed E. Tarabra, S. Pelengaris, M. Khan, A simple matter of life and death-the trials of postnatal beta-cell mass regulation. Int. J. Endocrinol. 2012, 516718 (2012)PubMed
9.
go back to reference B. Xia, X.R. Zhan, R. Yi, B. Yang, Can pancreatic duct-derived progenitors be a source of islet regeneration? Biochem. Biophys. Res. Commun. 383(4), 383–385 (2009)PubMedCrossRef B. Xia, X.R. Zhan, R. Yi, B. Yang, Can pancreatic duct-derived progenitors be a source of islet regeneration? Biochem. Biophys. Res. Commun. 383(4), 383–385 (2009)PubMedCrossRef
10.
go back to reference C. Demeterco, E. Hao, S.H. Lee, P. Itkin-Ansari, F. Levine, Adult human beta-cell neogenesis? Diabetes Obes. Metab. 11(Suppl. 4), 46–53 (2009)PubMedCrossRef C. Demeterco, E. Hao, S.H. Lee, P. Itkin-Ansari, F. Levine, Adult human beta-cell neogenesis? Diabetes Obes. Metab. 11(Suppl. 4), 46–53 (2009)PubMedCrossRef
11.
go back to reference P.A. Lysy, G.C. Weir, S. Bonner-Weir, Concise review: pancreas regeneration: recent advances and perspectives. Stem Cells Transl. Med. 1(2), 150–159 (2012)PubMedCrossRef P.A. Lysy, G.C. Weir, S. Bonner-Weir, Concise review: pancreas regeneration: recent advances and perspectives. Stem Cells Transl. Med. 1(2), 150–159 (2012)PubMedCrossRef
12.
go back to reference L. Bouwens, I. Rooman, Regulation of pancreatic beta-cell mass. Physiol. Rev. 85(4), 1255–1270 (2005)PubMedCrossRef L. Bouwens, I. Rooman, Regulation of pancreatic beta-cell mass. Physiol. Rev. 85(4), 1255–1270 (2005)PubMedCrossRef
13.
go back to reference F.M. Ashcroft, P. Rorsman, Diabetes mellitus and the beta cell: the last ten years. Cell 148(6), 1160–1171 (2012)PubMedCrossRef F.M. Ashcroft, P. Rorsman, Diabetes mellitus and the beta cell: the last ten years. Cell 148(6), 1160–1171 (2012)PubMedCrossRef
14.
go back to reference Wu, J., Wu, J.J., Yang, L.J., Wei, L.X., Zou D.J.: Rosiglitazone protects against palmitate-induced pancreatic beta-cell death by activation of autophagy via 5′-AMP-activated protein kinase modulation. Endocrine (2012). doi:10.1007/s12020-012-9826-5 Wu, J., Wu, J.J., Yang, L.J., Wei, L.X., Zou D.J.: Rosiglitazone protects against palmitate-induced pancreatic beta-cell death by activation of autophagy via 5′-AMP-activated protein kinase modulation. Endocrine (2012). doi:10.​1007/​s12020-012-9826-5
15.
go back to reference M.Y. Donath, P.A. Halban, Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications. Diabetologia 47(3), 581–589 (2004)PubMedCrossRef M.Y. Donath, P.A. Halban, Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications. Diabetologia 47(3), 581–589 (2004)PubMedCrossRef
16.
go back to reference D.R. Green, B. Victor, The pantheon of the fallen: why are there so many forms of cell death? Trends Cell Biol. 22(11), 555–556 (2012)PubMedCrossRef D.R. Green, B. Victor, The pantheon of the fallen: why are there so many forms of cell death? Trends Cell Biol. 22(11), 555–556 (2012)PubMedCrossRef
17.
go back to reference D. Choi, M. Woo, Executioners of apoptosis in pancreatic beta-cells: not just for cell death. Am. J. Physiol. Endocrinol. Metab. 298(4), E735–E741 (2010)PubMedCrossRef D. Choi, M. Woo, Executioners of apoptosis in pancreatic beta-cells: not just for cell death. Am. J. Physiol. Endocrinol. Metab. 298(4), E735–E741 (2010)PubMedCrossRef
18.
go back to reference E.L. Bradley, A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. Arch. Surg. 128(5), 586–590 (1993)PubMedCrossRef E.L. Bradley, A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. Arch. Surg. 128(5), 586–590 (1993)PubMedCrossRef
19.
go back to reference K.Y. Hur, H.S. Jung, M.S. Lee, Role of autophagy in beta-cell function and mass. Diabetes Obes. Metab. 12(Suppl. 2), 20–26 (2010)PubMedCrossRef K.Y. Hur, H.S. Jung, M.S. Lee, Role of autophagy in beta-cell function and mass. Diabetes Obes. Metab. 12(Suppl. 2), 20–26 (2010)PubMedCrossRef
20.
go back to reference G. Las, O.S. Shirihai, The role of autophagy in beta-cell lipotoxicity and type 2 diabetes. Diabetes Obes. Metab. 12(Suppl. 2), 15–19 (2010)PubMedCrossRef G. Las, O.S. Shirihai, The role of autophagy in beta-cell lipotoxicity and type 2 diabetes. Diabetes Obes. Metab. 12(Suppl. 2), 15–19 (2010)PubMedCrossRef
21.
go back to reference M. Masini, M. Bugliani, R. Lupi, S. Del Guerra, U. Boggi, F. Filipponi, L. Marselli, P. Masiello, P. Marchetti, Autophagy in human type 2 diabetes pancreatic beta cells. Diabetologia 52(6), 1083–1086 (2009)PubMedCrossRef M. Masini, M. Bugliani, R. Lupi, S. Del Guerra, U. Boggi, F. Filipponi, L. Marselli, P. Masiello, P. Marchetti, Autophagy in human type 2 diabetes pancreatic beta cells. Diabetologia 52(6), 1083–1086 (2009)PubMedCrossRef
22.
go back to reference S.J. Dixon, K.M. Lemberg, M.R. Lamprecht, R. Skouta, E.M. Zaitsev, C.E. Gleason, D.N. Patel, A.J. Bauer, A.M. Cantley, W.S. Yang, B. Morrison, B.R. Stockwell, Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5), 1060–1072 (2012)PubMedCrossRef S.J. Dixon, K.M. Lemberg, M.R. Lamprecht, R. Skouta, E.M. Zaitsev, C.E. Gleason, D.N. Patel, A.J. Bauer, A.M. Cantley, W.S. Yang, B. Morrison, B.R. Stockwell, Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5), 1060–1072 (2012)PubMedCrossRef
23.
24.
go back to reference B.Z. Stanger, A.J. Tanaka, D.A. Melton, Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver. Nature 445(7130), 886–891 (2007)PubMedCrossRef B.Z. Stanger, A.J. Tanaka, D.A. Melton, Organ size is limited by the number of embryonic progenitor cells in the pancreas but not the liver. Nature 445(7130), 886–891 (2007)PubMedCrossRef
25.
go back to reference B.E. Gregg, P.C. Moore, D. Demozay, B.A. Hall, M. Li, A. Husain, A.J. Wright, M.A. Atkinson, C.J. Rhodes, Formation of a human beta-cell population within pancreatic islets is set early in life. J. Clin. Endocrinol. Metab. 97(9), 3197–3206 (2012)PubMedCrossRef B.E. Gregg, P.C. Moore, D. Demozay, B.A. Hall, M. Li, A. Husain, A.J. Wright, M.A. Atkinson, C.J. Rhodes, Formation of a human beta-cell population within pancreatic islets is set early in life. J. Clin. Endocrinol. Metab. 97(9), 3197–3206 (2012)PubMedCrossRef
26.
go back to reference M.E. Cerf, Parental high-fat programming of offspring development, health and beta-cells. Islets 3(3), 118–120 (2011)PubMedCrossRef M.E. Cerf, Parental high-fat programming of offspring development, health and beta-cells. Islets 3(3), 118–120 (2011)PubMedCrossRef
27.
go back to reference Y. Zhang, Y. Zhang, R.N. Bone, W. Cui, J.B. Peng, G.P. Siegal, H. Wang, H. Wu, Regeneration of pancreatic non beta endocrine cells in adult mice following a single diabetes-inducing dose of streptozotocin. PLoS ONE 7(5), e36675 (2012)PubMedCrossRef Y. Zhang, Y. Zhang, R.N. Bone, W. Cui, J.B. Peng, G.P. Siegal, H. Wang, H. Wu, Regeneration of pancreatic non beta endocrine cells in adult mice following a single diabetes-inducing dose of streptozotocin. PLoS ONE 7(5), e36675 (2012)PubMedCrossRef
28.
29.
go back to reference I. Chambers, A. Smith, Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23(43), 7150–7160 (2004)PubMedCrossRef I. Chambers, A. Smith, Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23(43), 7150–7160 (2004)PubMedCrossRef
30.
go back to reference A.J. Becker, E.A. McCulloch, J.E. Till, Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197, 452–454 (1963)PubMedCrossRef A.J. Becker, E.A. McCulloch, J.E. Till, Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197, 452–454 (1963)PubMedCrossRef
31.
go back to reference O. Tavana, C. Zhu, Too many breaks (brakes): pancreatic beta-cell senescence leads to diabetes. Cell Cycle 10(15), 2471–2484 (2011)PubMedCrossRef O. Tavana, C. Zhu, Too many breaks (brakes): pancreatic beta-cell senescence leads to diabetes. Cell Cycle 10(15), 2471–2484 (2011)PubMedCrossRef
32.
go back to reference Y. Dor, J. Brown, O.I. Martinez, D.A. Melton, Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429(6987), 41–46 (2004)PubMedCrossRef Y. Dor, J. Brown, O.I. Martinez, D.A. Melton, Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429(6987), 41–46 (2004)PubMedCrossRef
33.
go back to reference Y. Saisho, E. Manesso, A.E. Butler, R. Galasso, K. Kavanagh, M. Flynn, L. Zhang, P. Clark, T. Gurlo, G.M. Toffolo, C. Cobelli, J.D. Wagner, P.C. Butler, Ongoing beta-cell turnover in adult nonhuman primates is not adaptively increased in streptozotocin-induced diabetes. Diabetes 60(3), 848–856 (2011)PubMedCrossRef Y. Saisho, E. Manesso, A.E. Butler, R. Galasso, K. Kavanagh, M. Flynn, L. Zhang, P. Clark, T. Gurlo, G.M. Toffolo, C. Cobelli, J.D. Wagner, P.C. Butler, Ongoing beta-cell turnover in adult nonhuman primates is not adaptively increased in streptozotocin-induced diabetes. Diabetes 60(3), 848–856 (2011)PubMedCrossRef
34.
go back to reference L. Bouwens, D.G. Pipeleers, Extra-insular beta cells associated with ductules are frequent in adult human pancreas. Diabetologia 41(6), 629–633 (1998)PubMedCrossRef L. Bouwens, D.G. Pipeleers, Extra-insular beta cells associated with ductules are frequent in adult human pancreas. Diabetologia 41(6), 629–633 (1998)PubMedCrossRef
35.
go back to reference J.J. Meier, J.C. Lin, A.E. Butler, R. Galasso, D.S. Martinez, P.C. Butler, Direct evidence of attempted beta cell regeneration in an 89-year-old patient with recent-onset type 1 diabetes. Diabetologia 49(8), 1838–1844 (2006)PubMedCrossRef J.J. Meier, J.C. Lin, A.E. Butler, R. Galasso, D.S. Martinez, P.C. Butler, Direct evidence of attempted beta cell regeneration in an 89-year-old patient with recent-onset type 1 diabetes. Diabetologia 49(8), 1838–1844 (2006)PubMedCrossRef
36.
go back to reference M. Teta, M.M. Rankin, S.Y. Long, G.M. Stein, J.A. Kushner, Growth and regeneration of adult beta cells does not involve specialized progenitors. Dev. Cell 12(5), 817–826 (2007)PubMedCrossRef M. Teta, M.M. Rankin, S.Y. Long, G.M. Stein, J.A. Kushner, Growth and regeneration of adult beta cells does not involve specialized progenitors. Dev. Cell 12(5), 817–826 (2007)PubMedCrossRef
37.
go back to reference H. Liu, Y. Guz, M.H. Kedees, J. Winkler, G. Teitelman, Precursor cells in mouse islets generate new beta-cells in vivo during aging and after islet injury. Endocrinology 151(2), 520–528 (2010)PubMedCrossRef H. Liu, Y. Guz, M.H. Kedees, J. Winkler, G. Teitelman, Precursor cells in mouse islets generate new beta-cells in vivo during aging and after islet injury. Endocrinology 151(2), 520–528 (2010)PubMedCrossRef
38.
go back to reference X. Xu, J. D’Hoker, G. Stange, S. Bonne, L.N. De, X. Xiao, M. Van De Casteele, G. Mellitzer, Z. Ling, D. Pipeleers, L. Bouwens, R. Scharfmann, G. Gradwohl, H. Heimberg, Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 132(2), 197–207 (2008)PubMedCrossRef X. Xu, J. D’Hoker, G. Stange, S. Bonne, L.N. De, X. Xiao, M. Van De Casteele, G. Mellitzer, Z. Ling, D. Pipeleers, L. Bouwens, R. Scharfmann, G. Gradwohl, H. Heimberg, Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell 132(2), 197–207 (2008)PubMedCrossRef
39.
go back to reference F. Thorel, V. Nepote, I. Avril, K. Kohno, R. Desgraz, S. Chera, P.L. Herrera, Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature 464(7292), 1149–1154 (2010)PubMedCrossRef F. Thorel, V. Nepote, I. Avril, K. Kohno, R. Desgraz, S. Chera, P.L. Herrera, Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature 464(7292), 1149–1154 (2010)PubMedCrossRef
40.
go back to reference Z. Liu, W. Kim, Z. Chen, Y.K. Shin, O.D. Carlson, J.L. Fiori, Insulin and glucagon regulate pancreatic alpha-cell proliferation. PLoS ONE 6(1), e16096 (2011)PubMedCrossRef Z. Liu, W. Kim, Z. Chen, Y.K. Shin, O.D. Carlson, J.L. Fiori, Insulin and glucagon regulate pancreatic alpha-cell proliferation. PLoS ONE 6(1), e16096 (2011)PubMedCrossRef
41.
go back to reference L.C. Murtaugh, D.A. Melton, Genes, signals, and lineages in pancreas development. Annu. Rev. Cell Dev. Biol. 19, 71–89 (2003)PubMedCrossRef L.C. Murtaugh, D.A. Melton, Genes, signals, and lineages in pancreas development. Annu. Rev. Cell Dev. Biol. 19, 71–89 (2003)PubMedCrossRef
42.
go back to reference Q. Zhou, J. Brown, A. Kanarek, J. Rajagopal, D.A. Melton, In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455(7213), 627–632 (2008)PubMedCrossRef Q. Zhou, J. Brown, A. Kanarek, J. Rajagopal, D.A. Melton, In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature 455(7213), 627–632 (2008)PubMedCrossRef
43.
go back to reference E. Akinci, A. Banga, L.V. Greder, J.R. Dutton, J.M. Slack, Reprogramming of pancreatic exocrine cells towards a beta cell character using Pdx1, Ngn3 and MafA. Biochem. J. 442(3), 539–550 (2012)PubMedCrossRef E. Akinci, A. Banga, L.V. Greder, J.R. Dutton, J.M. Slack, Reprogramming of pancreatic exocrine cells towards a beta cell character using Pdx1, Ngn3 and MafA. Biochem. J. 442(3), 539–550 (2012)PubMedCrossRef
44.
go back to reference S. Bonner-Weir, A. Inada, S. Yatoh, W.C. Li, T. Aye, E. Toschi, A. Sharma, Transdifferentiation of pancreatic ductal cells to endocrine beta-cells. Biochem. Soc. Trans. 36(Pt. 3), 353–356 (2008)PubMedCrossRef S. Bonner-Weir, A. Inada, S. Yatoh, W.C. Li, T. Aye, E. Toschi, A. Sharma, Transdifferentiation of pancreatic ductal cells to endocrine beta-cells. Biochem. Soc. Trans. 36(Pt. 3), 353–356 (2008)PubMedCrossRef
45.
go back to reference J. Shen, Y. Cheng, Q. Han, Y. Mu, W. Han, Generating insulin-producing cells for diabetic therapy: existing strategies and new development. Ageing Res. Rev. 12(2), 469–478 (2013)PubMedCrossRef J. Shen, Y. Cheng, Q. Han, Y. Mu, W. Han, Generating insulin-producing cells for diabetic therapy: existing strategies and new development. Ageing Res. Rev. 12(2), 469–478 (2013)PubMedCrossRef
46.
go back to reference M.E. Cerf, C.S. Chapman, J. Louw, High-fat programming of hyperglycemia, hyperinsulinemia, insulin resistance, hyperleptinemia, and altered islet architecture in 3-month-old wistar rats. ISRN Endocrinol. 2012, 627270 (2012)PubMed M.E. Cerf, C.S. Chapman, J. Louw, High-fat programming of hyperglycemia, hyperinsulinemia, insulin resistance, hyperleptinemia, and altered islet architecture in 3-month-old wistar rats. ISRN Endocrinol. 2012, 627270 (2012)PubMed
47.
go back to reference N. Swales, G.A. Martens, S. Bonne, Y. Heremans, R. Borup, M. Van De Casteele, Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming. PLoS ONE 7(5), e37055 (2012)PubMedCrossRef N. Swales, G.A. Martens, S. Bonne, Y. Heremans, R. Borup, M. Van De Casteele, Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming. PLoS ONE 7(5), e37055 (2012)PubMedCrossRef
48.
go back to reference A.M. Jamal, M. Lipsett, R. Sladek, S. Laganiere, S. Hanley, L. Rosenberg, Morphogenetic plasticity of adult human pancreatic islets of Langerhans. Cell Death Differ. 12(7), 702–712 (2005)PubMedCrossRef A.M. Jamal, M. Lipsett, R. Sladek, S. Laganiere, S. Hanley, L. Rosenberg, Morphogenetic plasticity of adult human pancreatic islets of Langerhans. Cell Death Differ. 12(7), 702–712 (2005)PubMedCrossRef
49.
go back to reference L. Shu, K. Zien, G. Gutjahr, J. Oberholzer, F. Pattou, J. Kerr-Conte, K. Maedler, TCF7L2 promotes beta cell regeneration in human and mouse pancreas. Diabetologia 55(12), 3296–3307 (2012)PubMedCrossRef L. Shu, K. Zien, G. Gutjahr, J. Oberholzer, F. Pattou, J. Kerr-Conte, K. Maedler, TCF7L2 promotes beta cell regeneration in human and mouse pancreas. Diabetologia 55(12), 3296–3307 (2012)PubMedCrossRef
50.
go back to reference R.M. Baertschiger, D. Bosco, P. Morel, V. Serre-Beinier, T. Berney, L.H. Buhler, C. Gonelle-Gispert, Mesenchymal stem cells derived from human exocrine pancreas express transcription factors implicated in beta-cell development. Pancreas 37(1), 75–84 (2008)PubMedCrossRef R.M. Baertschiger, D. Bosco, P. Morel, V. Serre-Beinier, T. Berney, L.H. Buhler, C. Gonelle-Gispert, Mesenchymal stem cells derived from human exocrine pancreas express transcription factors implicated in beta-cell development. Pancreas 37(1), 75–84 (2008)PubMedCrossRef
51.
go back to reference K.L. Seeberger, J.M. Dufour, A.M. Shapiro, J.R. Lakey, R.V. Rajotte, G.S. Korbutt, Expansion of mesenchymal stem cells from human pancreatic ductal epithelium. Lab. Invest. 86(2), 141–153 (2006)PubMedCrossRef K.L. Seeberger, J.M. Dufour, A.M. Shapiro, J.R. Lakey, R.V. Rajotte, G.S. Korbutt, Expansion of mesenchymal stem cells from human pancreatic ductal epithelium. Lab. Invest. 86(2), 141–153 (2006)PubMedCrossRef
52.
go back to reference J.M. Rossi, N.R. Dunn, B.L. Hogan, K.S. Zaret, Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. Genes Dev. 15(15), 1998–2009 (2001)PubMedCrossRef J.M. Rossi, N.R. Dunn, B.L. Hogan, K.S. Zaret, Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm. Genes Dev. 15(15), 1998–2009 (2001)PubMedCrossRef
53.
go back to reference G. Deutsch, J. Jung, M. Zheng, J. Lora, K.S. Zaret, A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development 128(6), 871–881 (2001)PubMed G. Deutsch, J. Jung, M. Zheng, J. Lora, K.S. Zaret, A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development 128(6), 871–881 (2001)PubMed
54.
go back to reference L. Yang, S. Li, H. Hatch, K. Ahrens, J.G. Cornelius, B.E. Petersen, In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc. Natl. Acad. Sci. U.S.A. 99(12), 8078–8083 (2002)PubMedCrossRef L. Yang, S. Li, H. Hatch, K. Ahrens, J.G. Cornelius, B.E. Petersen, In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc. Natl. Acad. Sci. U.S.A. 99(12), 8078–8083 (2002)PubMedCrossRef
55.
go back to reference H. Kaneto, Y. Nakatani, T. Miyatsuka, T.A. Matsuoka, M. Matsuhisa, M. Hori, PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. Diabetes 54(4), 1009–1022 (2005)PubMedCrossRef H. Kaneto, Y. Nakatani, T. Miyatsuka, T.A. Matsuoka, M. Matsuhisa, M. Hori, PDX-1/VP16 fusion protein, together with NeuroD or Ngn3, markedly induces insulin gene transcription and ameliorates glucose tolerance. Diabetes 54(4), 1009–1022 (2005)PubMedCrossRef
56.
go back to reference Y.D. Song, E.J. Lee, P. Yashar, L.E. Pfaff, S.Y. Kim, J.L. Jameson, Islet cell differentiation in liver by combinatorial expression of transcription factors neurogenin-3, BETA2, and RIPE3b1. Biochem. Biophys. Res. Commun. 354(2), 334–339 (2007)PubMedCrossRef Y.D. Song, E.J. Lee, P. Yashar, L.E. Pfaff, S.Y. Kim, J.L. Jameson, Islet cell differentiation in liver by combinatorial expression of transcription factors neurogenin-3, BETA2, and RIPE3b1. Biochem. Biophys. Res. Commun. 354(2), 334–339 (2007)PubMedCrossRef
57.
go back to reference H. Motoyama, S. Ogawa, A. Kubo, S. Miwa, J. Nakayama, Y. Tagawa, In vitro reprogramming of adult hepatocytes into insulin-producing cells without viral vectors. Biochem. Biophys. Res. Commun. 385(1), 123–128 (2009)PubMedCrossRef H. Motoyama, S. Ogawa, A. Kubo, S. Miwa, J. Nakayama, Y. Tagawa, In vitro reprogramming of adult hepatocytes into insulin-producing cells without viral vectors. Biochem. Biophys. Res. Commun. 385(1), 123–128 (2009)PubMedCrossRef
58.
go back to reference V.K. Ramiya, M. Maraist, K.E. Arfors, D.A. Schatz, A.B. Peck, J.G. Cornelius, Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat. Med. 6(3), 278–282 (2000)PubMedCrossRef V.K. Ramiya, M. Maraist, K.E. Arfors, D.A. Schatz, A.B. Peck, J.G. Cornelius, Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat. Med. 6(3), 278–282 (2000)PubMedCrossRef
59.
go back to reference V. Yechoor, V. Liu, C. Espiritu, A. Paul, K. Oka, H. Kojima, L. Chan, Neurogenin3 is sufficient for transdetermination of hepatic progenitor cells into neo-islets in vivo but not transdifferentiation of hepatocytes. Dev. Cell 16(3), 358–373 (2009)PubMedCrossRef V. Yechoor, V. Liu, C. Espiritu, A. Paul, K. Oka, H. Kojima, L. Chan, Neurogenin3 is sufficient for transdetermination of hepatic progenitor cells into neo-islets in vivo but not transdifferentiation of hepatocytes. Dev. Cell 16(3), 358–373 (2009)PubMedCrossRef
60.
go back to reference C. Rowe, C.E. Goldring, N.R. Kitteringham, R.E. Jenkins, B.S. Lane, C. Sanderson, V. Elliott, V. Platt, P. Metcalfe, B.K. Park, Network analysis of primary hepatocyte dedifferentiation using a shotgun proteomics approach. J. Proteome Res. 9(5), 2658–2668 (2010)PubMedCrossRef C. Rowe, C.E. Goldring, N.R. Kitteringham, R.E. Jenkins, B.S. Lane, C. Sanderson, V. Elliott, V. Platt, P. Metcalfe, B.K. Park, Network analysis of primary hepatocyte dedifferentiation using a shotgun proteomics approach. J. Proteome Res. 9(5), 2658–2668 (2010)PubMedCrossRef
61.
go back to reference H. Edlund, Pancreatic organogenesis–developmental mechanisms and implications for therapy. Nat. Rev. Genet. 3(7), 524–532 (2002)PubMedCrossRef H. Edlund, Pancreatic organogenesis–developmental mechanisms and implications for therapy. Nat. Rev. Genet. 3(7), 524–532 (2002)PubMedCrossRef
62.
go back to reference J.F. Habener, D.M. Kemp, M.K. Thomas, Minireview: transcriptional regulation in pancreatic development. Endocrinology 146(3), 1025–1034 (2005)PubMedCrossRef J.F. Habener, D.M. Kemp, M.K. Thomas, Minireview: transcriptional regulation in pancreatic development. Endocrinology 146(3), 1025–1034 (2005)PubMedCrossRef
63.
go back to reference T. Kuwabara, M.N. Kagalwala, Y. Onuma, Y. Ito, M. Warashina, K. Terashima, T. Sanosaka, K. Nakashima, F.H. Gage, M. Asashima, Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb. EMBO Mol. Med. 3(12), 742–754 (2011)PubMedCrossRef T. Kuwabara, M.N. Kagalwala, Y. Onuma, Y. Ito, M. Warashina, K. Terashima, T. Sanosaka, K. Nakashima, F.H. Gage, M. Asashima, Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb. EMBO Mol. Med. 3(12), 742–754 (2011)PubMedCrossRef
64.
go back to reference J.L. Plank, N.A. Mundell, A.Y. Frist, A.W. LeGrone, T. Kim, M.A. Musser, T.J. Walter, P.A. Labosky, Influence and timing of arrival of murine neural crest on pancreatic beta cell development and maturation. Dev. Biol. 349(2), 321–330 (2011)PubMedCrossRef J.L. Plank, N.A. Mundell, A.Y. Frist, A.W. LeGrone, T. Kim, M.A. Musser, T.J. Walter, P.A. Labosky, Influence and timing of arrival of murine neural crest on pancreatic beta cell development and maturation. Dev. Biol. 349(2), 321–330 (2011)PubMedCrossRef
65.
go back to reference N. Nekrep, J. Wang, T. Miyatsuka, M.S. German, Signals from the neural crest regulate beta-cell mass in the pancreas. Development 135(12), 2151–2160 (2008)PubMedCrossRef N. Nekrep, J. Wang, T. Miyatsuka, M.S. German, Signals from the neural crest regulate beta-cell mass in the pancreas. Development 135(12), 2151–2160 (2008)PubMedCrossRef
66.
go back to reference R.E. Burris, M. Hebrok, Pancreatic innervation in mouse development and beta-cell regeneration. Neuroscience 150(3), 592–602 (2007)PubMedCrossRef R.E. Burris, M. Hebrok, Pancreatic innervation in mouse development and beta-cell regeneration. Neuroscience 150(3), 592–602 (2007)PubMedCrossRef
67.
go back to reference G. Grouwels, S. Vasylovska, J. Olerud, G. Leuckx, A. Ngamjariyawat, Y. Yuchi, L. Jansson, M. Van De Casteele, E.N. Kozlova, H. Heimberg, Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells. Diabetologia 55(7), 2016–2025 (2012)PubMedCrossRef G. Grouwels, S. Vasylovska, J. Olerud, G. Leuckx, A. Ngamjariyawat, Y. Yuchi, L. Jansson, M. Van De Casteele, E.N. Kozlova, H. Heimberg, Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells. Diabetologia 55(7), 2016–2025 (2012)PubMedCrossRef
68.
go back to reference A.M. Holland, L.J. Gonez, L.C. Harrison, Progenitor cells in the adult pancreas. Diabetes Metab. Res. Rev. 20(1), 13–27 (2004)PubMedCrossRef A.M. Holland, L.J. Gonez, L.C. Harrison, Progenitor cells in the adult pancreas. Diabetes Metab. Res. Rev. 20(1), 13–27 (2004)PubMedCrossRef
69.
go back to reference S. Bonner-Weir, E. Toschi, A. Inada, P. Reitz, S.Y. Fonseca, T. Aye, A. Sharma, The pancreatic ductal epithelium serves as a potential pool of progenitor cells. Pediatr. Diabetes 5(Suppl. 2), 16–22 (2004)PubMedCrossRef S. Bonner-Weir, E. Toschi, A. Inada, P. Reitz, S.Y. Fonseca, T. Aye, A. Sharma, The pancreatic ductal epithelium serves as a potential pool of progenitor cells. Pediatr. Diabetes 5(Suppl. 2), 16–22 (2004)PubMedCrossRef
70.
go back to reference C.S. Potten, M. Loeffler, Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 110(4), 1001–1020 (1990)PubMed C.S. Potten, M. Loeffler, Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 110(4), 1001–1020 (1990)PubMed
71.
72.
go back to reference S. Weiss, B.A. Reynolds, A.L. Vescovi, C. Morshead, C.G. Craig, D. van der Kooy, Is there a neural stem cell in the mammalian forebrain? Trends Neurosci. 19(9), 387–393 (1996)PubMedCrossRef S. Weiss, B.A. Reynolds, A.L. Vescovi, C. Morshead, C.G. Craig, D. van der Kooy, Is there a neural stem cell in the mammalian forebrain? Trends Neurosci. 19(9), 387–393 (1996)PubMedCrossRef
73.
go back to reference N.J. Blyth, Mechanisms and techniques of reprogramming-using PDX-1 homeobox protein as a novel treatment of insulin dependent diabetes mellitus. Diabetes Metab. Syndr. 6(2), 113–119 (2012)PubMedCrossRef N.J. Blyth, Mechanisms and techniques of reprogramming-using PDX-1 homeobox protein as a novel treatment of insulin dependent diabetes mellitus. Diabetes Metab. Syndr. 6(2), 113–119 (2012)PubMedCrossRef
74.
go back to reference E. Manesso, G.M. Toffolo, Y. Saisho, A.E. Butler, A.V. Matveyenko, C. Cobelli, P.C. Butler, Dynamics of beta-cell turnover: evidence for beta-cell turnover and regeneration from sources of beta-cells other than beta-cell replication in the HIP rat. Am. J. Physiol. Endocrinol. Metab. 297(2), E323–E330 (2009)PubMedCrossRef E. Manesso, G.M. Toffolo, Y. Saisho, A.E. Butler, A.V. Matveyenko, C. Cobelli, P.C. Butler, Dynamics of beta-cell turnover: evidence for beta-cell turnover and regeneration from sources of beta-cells other than beta-cell replication in the HIP rat. Am. J. Physiol. Endocrinol. Metab. 297(2), E323–E330 (2009)PubMedCrossRef
75.
go back to reference S.R. Smukler, M.E. Arntfield, R. Razavi, G. Bikopoulos, P. Karpowicz, R. Seaberg, F. Dai, S. Lee, R. Ahrens, P.E. Fraser, M.B. Wheeler, D. van der Kooy, The adult mouse and human pancreas contain rare multipotent stem cells that express insulin. Cell Stem Cell 8(3), 281–293 (2011)PubMedCrossRef S.R. Smukler, M.E. Arntfield, R. Razavi, G. Bikopoulos, P. Karpowicz, R. Seaberg, F. Dai, S. Lee, R. Ahrens, P.E. Fraser, M.B. Wheeler, D. van der Kooy, The adult mouse and human pancreas contain rare multipotent stem cells that express insulin. Cell Stem Cell 8(3), 281–293 (2011)PubMedCrossRef
76.
go back to reference R.M. Seaberg, S.R. Smukler, T.J. Kieffer, G. Enikolopov, Z. Asghar, M.B. Wheeler, G. Korbutt, D. van der Kooy, Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat. Biotechnol. 22(9), 1115–1124 (2004)PubMedCrossRef R.M. Seaberg, S.R. Smukler, T.J. Kieffer, G. Enikolopov, Z. Asghar, M.B. Wheeler, G. Korbutt, D. van der Kooy, Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages. Nat. Biotechnol. 22(9), 1115–1124 (2004)PubMedCrossRef
77.
go back to reference M.A. Goodell, K. Brose, G. Paradis, A.S. Conner, R.C. Mulligan, Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J. Exp. Med. 183(4), 1797–1806 (1996)PubMedCrossRef M.A. Goodell, K. Brose, G. Paradis, A.S. Conner, R.C. Mulligan, Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J. Exp. Med. 183(4), 1797–1806 (1996)PubMedCrossRef
78.
go back to reference I. Banakh, L.J. Gonez, R.M. Sutherland, G. Naselli, L.C. Harrison, Adult pancreas side population cells expand after beta cell injury and are a source of insulin-secreting cells. PLoS ONE 7(11), e48977 (2012)PubMedCrossRef I. Banakh, L.J. Gonez, R.M. Sutherland, G. Naselli, L.C. Harrison, Adult pancreas side population cells expand after beta cell injury and are a source of insulin-secreting cells. PLoS ONE 7(11), e48977 (2012)PubMedCrossRef
79.
go back to reference J. Dominguez-Bendala, C. Ricordi, Present and future cell therapies for pancreatic beta cell replenishment. World J. Gastroenterol. 18(47), 6876–6884 (2012)PubMedCrossRef J. Dominguez-Bendala, C. Ricordi, Present and future cell therapies for pancreatic beta cell replenishment. World J. Gastroenterol. 18(47), 6876–6884 (2012)PubMedCrossRef
80.
go back to reference L. Landsman, A. Nijagal, T.J. Whitchurch, R.L. Vanderlaan, W.E. Zimmer, T.C. Mackenzie, M. Hebrok, Pancreatic mesenchyme regulates epithelial organogenesis throughout development. PLoS Biol. 9(9), e1001143 (2011)PubMedCrossRef L. Landsman, A. Nijagal, T.J. Whitchurch, R.L. Vanderlaan, W.E. Zimmer, T.C. Mackenzie, M. Hebrok, Pancreatic mesenchyme regulates epithelial organogenesis throughout development. PLoS Biol. 9(9), e1001143 (2011)PubMedCrossRef
81.
go back to reference J.M. Slack, Developmental biology of the pancreas. Development 121(6), 1569–1580 (1995)PubMed J.M. Slack, Developmental biology of the pancreas. Development 121(6), 1569–1580 (1995)PubMed
82.
go back to reference S.C. Hanley, E. Austin, B. Assouline-Thomas, J. Kapeluto, J. Blaichman, M. Moosavi, M. Petropavlovskaia, L. Rosenberg, Beta-cell mass dynamics and islet cell plasticity in human type 2 diabetes. Endocrinology 151(4), 1462–1472 (2010)PubMedCrossRef S.C. Hanley, E. Austin, B. Assouline-Thomas, J. Kapeluto, J. Blaichman, M. Moosavi, M. Petropavlovskaia, L. Rosenberg, Beta-cell mass dynamics and islet cell plasticity in human type 2 diabetes. Endocrinology 151(4), 1462–1472 (2010)PubMedCrossRef
83.
go back to reference M. Karaca, C. Magnan, C. Kargar, Functional pancreatic beta-cell mass: involvement in type 2 diabetes and therapeutic intervention. Diabetes Metab. 35(2), 77–84 (2009)PubMedCrossRef M. Karaca, C. Magnan, C. Kargar, Functional pancreatic beta-cell mass: involvement in type 2 diabetes and therapeutic intervention. Diabetes Metab. 35(2), 77–84 (2009)PubMedCrossRef
84.
go back to reference N. Kaiser, R. Nesher, M.Y. Donath, M. Fraenkel, V. Behar, C. Magnan, A. Ktorza, E. Cerasi, G. Leibowitz, Psammomys obesus, a model for environment-gene interactions in type 2 diabetes. Diabetes 54(Suppl. 2), S137–S144 (2005)PubMedCrossRef N. Kaiser, R. Nesher, M.Y. Donath, M. Fraenkel, V. Behar, C. Magnan, A. Ktorza, E. Cerasi, G. Leibowitz, Psammomys obesus, a model for environment-gene interactions in type 2 diabetes. Diabetes 54(Suppl. 2), S137–S144 (2005)PubMedCrossRef
85.
go back to reference C. Bernard, C. Thibault, M.F. Berthault, C. Magnan, C. Saulnier, B. Portha, W.F. Pralong, L. Penicaud, A. Ktorza, Pancreatic beta-cell regeneration after 48-h glucose infusion in mildly diabetic rats is not correlated with functional improvement. Diabetes 47(7), 1058–1065 (1998)PubMedCrossRef C. Bernard, C. Thibault, M.F. Berthault, C. Magnan, C. Saulnier, B. Portha, W.F. Pralong, L. Penicaud, A. Ktorza, Pancreatic beta-cell regeneration after 48-h glucose infusion in mildly diabetic rats is not correlated with functional improvement. Diabetes 47(7), 1058–1065 (1998)PubMedCrossRef
86.
87.
go back to reference M. Brissova, M. Blaha, C. Spear, W. Nicholson, A. Radhika, M. Shiota, Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis. Am. J. Physiol. Endocrinol. Metab. 288(4), 707–714 (2005)CrossRef M. Brissova, M. Blaha, C. Spear, W. Nicholson, A. Radhika, M. Shiota, Reduced PDX-1 expression impairs islet response to insulin resistance and worsens glucose homeostasis. Am. J. Physiol. Endocrinol. Metab. 288(4), 707–714 (2005)CrossRef
88.
go back to reference G. Kwon, C.A. Marshall, K.L. Pappan, M.S. Remedi, M.L. McDaniel, Signaling elements involved in the metabolic regulation of mTOR by nutrients, incretins, and growth factors in islets. Diabetes 53(3), S225–S232 (2004)PubMedCrossRef G. Kwon, C.A. Marshall, K.L. Pappan, M.S. Remedi, M.L. McDaniel, Signaling elements involved in the metabolic regulation of mTOR by nutrients, incretins, and growth factors in islets. Diabetes 53(3), S225–S232 (2004)PubMedCrossRef
89.
go back to reference L.C. Alonso, T. Yokoe, P. Zhang, D.K. Scott, S.K. Kim, C.P. O’Donnell, Glucose infusion in mice: a new model to induce beta-cell replication. Diabetes 56(7), 1792–1801 (2007)PubMedCrossRef L.C. Alonso, T. Yokoe, P. Zhang, D.K. Scott, S.K. Kim, C.P. O’Donnell, Glucose infusion in mice: a new model to induce beta-cell replication. Diabetes 56(7), 1792–1801 (2007)PubMedCrossRef
90.
go back to reference S. Bonner-Weir, D. Deery, J.L. Leahy, G.C. Weir, Compensatory growth of pancreatic beta-cells in adult rats after short-term glucose infusion. Diabetes 38(1), 49–53 (1989)PubMedCrossRef S. Bonner-Weir, D. Deery, J.L. Leahy, G.C. Weir, Compensatory growth of pancreatic beta-cells in adult rats after short-term glucose infusion. Diabetes 38(1), 49–53 (1989)PubMedCrossRef
91.
go back to reference M. Paris, C. Bernard-Kargar, M.F. Berthault, L. Bouwens, A. Ktorza, Specific and combined effects of insulin and glucose on functional pancreatic beta-cell mass in vivo in adult rats. Endocrinology 144(6), 2717–2727 (2003)PubMedCrossRef M. Paris, C. Bernard-Kargar, M.F. Berthault, L. Bouwens, A. Ktorza, Specific and combined effects of insulin and glucose on functional pancreatic beta-cell mass in vivo in adult rats. Endocrinology 144(6), 2717–2727 (2003)PubMedCrossRef
92.
go back to reference S. Porat, N. Weinberg-Corem, S. Tornovsky-Babaey, R. Schyr-Ben-Haroush, A. Hija, M. Stolovich-Rain, Control of pancreatic beta cell regeneration by glucose metabolism. Cell Metab. 13(4), 440–449 (2011)PubMedCrossRef S. Porat, N. Weinberg-Corem, S. Tornovsky-Babaey, R. Schyr-Ben-Haroush, A. Hija, M. Stolovich-Rain, Control of pancreatic beta cell regeneration by glucose metabolism. Cell Metab. 13(4), 440–449 (2011)PubMedCrossRef
93.
go back to reference K. Brennand, D. Huangfu, D. Melton, All beta cells contribute equally to islet growth and maintenance. PLoS Biol. 5(7), e163 (2007)PubMedCrossRef K. Brennand, D. Huangfu, D. Melton, All beta cells contribute equally to islet growth and maintenance. PLoS Biol. 5(7), e163 (2007)PubMedCrossRef
94.
go back to reference M. Brissova, A. Shostak, M. Shiota, P.O. Wiebe, G. Poffenberger, J. Kantz, Pancreatic islet production of vascular endothelial growth factor-a is essential for islet vascularization, revascularization, and function. Diabetes 55(11), 2974–2985 (2006)PubMedCrossRef M. Brissova, A. Shostak, M. Shiota, P.O. Wiebe, G. Poffenberger, J. Kantz, Pancreatic islet production of vascular endothelial growth factor-a is essential for islet vascularization, revascularization, and function. Diabetes 55(11), 2974–2985 (2006)PubMedCrossRef
95.
go back to reference D.G. Pipeleers, F.C. Schuit, P.A. In’t Veld, E. Maes, E.L. Hooghe-Peters, M. Van de Winkel, Interplay of nutrients and hormones in the regulation of insulin release. Endocrinology 117(3), 824–833 (1985)PubMedCrossRef D.G. Pipeleers, F.C. Schuit, P.A. In’t Veld, E. Maes, E.L. Hooghe-Peters, M. Van de Winkel, Interplay of nutrients and hormones in the regulation of insulin release. Endocrinology 117(3), 824–833 (1985)PubMedCrossRef
96.
go back to reference B. Thorens, Brain glucose sensing and neural regulation of insulin and glucagon secretion. Diabetes Obes. Metab. 13(1), 82–88 (2011)PubMedCrossRef B. Thorens, Brain glucose sensing and neural regulation of insulin and glucagon secretion. Diabetes Obes. Metab. 13(1), 82–88 (2011)PubMedCrossRef
97.
go back to reference Y. Zhang, M. Xiao, G. Niu, H. Tan, Mechanisms of oleic acid deterioration in insulin secretion: role in the pathogenesis of type 2 diabetes. Life Sci. 77(17), 2071–2081 (2005)PubMedCrossRef Y. Zhang, M. Xiao, G. Niu, H. Tan, Mechanisms of oleic acid deterioration in insulin secretion: role in the pathogenesis of type 2 diabetes. Life Sci. 77(17), 2071–2081 (2005)PubMedCrossRef
98.
go back to reference M.A. Kiraly, H.E. Bates, N.A. Kaniuk, J.T. Yue, J.H. Brumell, S.G. Matthews, M.C. Riddell, M. Vranic, Swim training prevents hyperglycemia in ZDF rats: mechanisms involved in the partial maintenance of beta-cell function. Am. J. Physiol. Endocrinol. Metab. 294(2), E271–E283 (2008)PubMedCrossRef M.A. Kiraly, H.E. Bates, N.A. Kaniuk, J.T. Yue, J.H. Brumell, S.G. Matthews, M.C. Riddell, M. Vranic, Swim training prevents hyperglycemia in ZDF rats: mechanisms involved in the partial maintenance of beta-cell function. Am. J. Physiol. Endocrinol. Metab. 294(2), E271–E283 (2008)PubMedCrossRef
99.
go back to reference C. Weyer, C. Bogardus, D.M. Mott, R.E. Pratley, The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J. Clin. Invest. 104(6), 787–794 (1999)PubMedCrossRef C. Weyer, C. Bogardus, D.M. Mott, R.E. Pratley, The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J. Clin. Invest. 104(6), 787–794 (1999)PubMedCrossRef
100.
go back to reference D.J. Withers, J.S. Gutierrez, H. Towery, D.J. Burks, J.M. Ren, S. Previs, Y. Zhang, D. Bernal, S. Pons, G.I. Shulman, S. Bonner-Weir, M.F. White, Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391(6670), 900–904 (1998)PubMedCrossRef D.J. Withers, J.S. Gutierrez, H. Towery, D.J. Burks, J.M. Ren, S. Previs, Y. Zhang, D. Bernal, S. Pons, G.I. Shulman, S. Bonner-Weir, M.F. White, Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391(6670), 900–904 (1998)PubMedCrossRef
Metadata
Title
Beta cell dynamics: beta cell replenishment, beta cell compensation and diabetes
Author
Marlon E. Cerf
Publication date
01-10-2013
Publisher
Springer US
Published in
Endocrine / Issue 2/2013
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-013-9917-y

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