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Erschienen in: Diabetologia 3/2004

01.03.2004 | For Debate

Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications

verfasst von: M. Y. Donath, P. A. Halban

Erschienen in: Diabetologia | Ausgabe 3/2004

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Abstract

Increasing evidence indicates that decreased functional beta-cell mass is the hallmark of both Type 1 and Type 2 diabetes. This underlies the absolute or relative insulin insufficiency in both conditions. In this For Debate, we consider the possible mechanisms responsible for beta-cell death and impaired function and their relative contribution to insulin insufficiency in diabetes. Beta-cell apoptosis and impaired proliferation consequent to hyperglycaemia is one pathway that could be operating in all forms of diabetes. Autoimmunity and other routes to beta-cell death are also considered. Recognition of decreased functional beta-cell mass and its overlapping multifactorial aetiology in diabetic states, leads us to propose a unifying classification of diabetes.
Literatur
1.
Zurück zum Zitat Yalow RS, Berson SA (1960) Plasma insulin concentrations in nondiabetic and early diabetic subjects: determinations by a new sensitive immuno-assay technic. Diabetes 9:254–260CrossRefPubMed Yalow RS, Berson SA (1960) Plasma insulin concentrations in nondiabetic and early diabetic subjects: determinations by a new sensitive immuno-assay technic. Diabetes 9:254–260CrossRefPubMed
2.
Zurück zum Zitat Karam JH, Grodsky G, Forsham PH (1963) Excessive insulin response to glucose in obese subjects as measured by immunochemical assay. Diabetes 12:197–204CrossRefPubMed Karam JH, Grodsky G, Forsham PH (1963) Excessive insulin response to glucose in obese subjects as measured by immunochemical assay. Diabetes 12:197–204CrossRefPubMed
3.
Zurück zum Zitat Cerasi E, Luft R (1967) Insulin response to glucose infusion in diabetic and non-diabetic monozygotic twin pairs. Genetic control of insulin response? Acta Endocrinol (Copenh) 55:330–345 Cerasi E, Luft R (1967) Insulin response to glucose infusion in diabetic and non-diabetic monozygotic twin pairs. Genetic control of insulin response? Acta Endocrinol (Copenh) 55:330–345
4.
Zurück zum Zitat DeFronzo RA (1988) Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37:667–687CrossRefPubMed DeFronzo RA (1988) Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37:667–687CrossRefPubMed
5.
Zurück zum Zitat Maclean N, Ogilvie RF (1955) Quantitative estimation of the pancreatic islet tissue in diabetic subjects. Diabetes 4:367–376CrossRefPubMed Maclean N, Ogilvie RF (1955) Quantitative estimation of the pancreatic islet tissue in diabetic subjects. Diabetes 4:367–376CrossRefPubMed
6.
Zurück zum Zitat Kloppel G, Lohr M, Habich K, Oberholzer M, Heitz PU (1985) Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. Surv Synth Pathol Res 4:110–125PubMed Kloppel G, Lohr M, Habich K, Oberholzer M, Heitz PU (1985) Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. Surv Synth Pathol Res 4:110–125PubMed
7.
Zurück zum Zitat Sakuraba H, Mizukami H, Yagihashi N, Wada R, Hanyu C, Yagihashi S (2002) Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients. Diabetologia 45:85–96CrossRefPubMed Sakuraba H, Mizukami H, Yagihashi N, Wada R, Hanyu C, Yagihashi S (2002) Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients. Diabetologia 45:85–96CrossRefPubMed
8.
Zurück zum Zitat Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with Type 2 diabetes. Diabetes 52:102–110CrossRefPubMed Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with Type 2 diabetes. Diabetes 52:102–110CrossRefPubMed
9.
Zurück zum Zitat Yoon KH, Ko SH, Cho JH et al. (2003) Selective beta-cell loss and alpha-cell expansion in patients with Type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 88:2300–2308CrossRefPubMed Yoon KH, Ko SH, Cho JH et al. (2003) Selective beta-cell loss and alpha-cell expansion in patients with Type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 88:2300–2308CrossRefPubMed
10.
Zurück zum Zitat Ward WK, LaCava EC, Paquette TL, Beard JC, Wallum BJ, Porte D (1987) Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance. Diabetologia 30:698–702CrossRefPubMed Ward WK, LaCava EC, Paquette TL, Beard JC, Wallum BJ, Porte D (1987) Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance. Diabetologia 30:698–702CrossRefPubMed
11.
Zurück zum Zitat Kahn SE, Halban PA (1997) Release of incompletely processed proinsulin is the cause of the disproportionate proinsulinemia of NIDDM. Diabetes 46:1725–1732CrossRefPubMed Kahn SE, Halban PA (1997) Release of incompletely processed proinsulin is the cause of the disproportionate proinsulinemia of NIDDM. Diabetes 46:1725–1732CrossRefPubMed
12.
Zurück zum Zitat Ward WK, Beard JC, Halter JB, Pfeifer MA, Porte D, Jr. (1984) Pathophysiology of insulin secretion in non-insulin-dependent diabetes mellitus. Diabetes Care 7:491–502CrossRefPubMed Ward WK, Beard JC, Halter JB, Pfeifer MA, Porte D, Jr. (1984) Pathophysiology of insulin secretion in non-insulin-dependent diabetes mellitus. Diabetes Care 7:491–502CrossRefPubMed
13.
Zurück zum Zitat Porksen N (2002) Early changes in beta-cell function and insulin pulsatility as predictors for type 2 diabetes. Diabetes Nutr Metab 15:9–14PubMed Porksen N (2002) Early changes in beta-cell function and insulin pulsatility as predictors for type 2 diabetes. Diabetes Nutr Metab 15:9–14PubMed
14.
Zurück zum Zitat Polonsky KS, Given BD, Hirsch LJ et al. (1988) Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. N Engl J Med 318:1231–1239CrossRefPubMed Polonsky KS, Given BD, Hirsch LJ et al. (1988) Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. N Engl J Med 318:1231–1239CrossRefPubMed
15.
Zurück zum Zitat Kahn SE (2003) The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 46:3–19CrossRefPubMed Kahn SE (2003) The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 46:3–19CrossRefPubMed
16.
Zurück zum Zitat Porksen N (2002) The in vivo regulation of pulsatile insulin secretion. Diabetologia 45:3–20CrossRefPubMed Porksen N (2002) The in vivo regulation of pulsatile insulin secretion. Diabetologia 45:3–20CrossRefPubMed
17.
Zurück zum Zitat Ward GM, Walters JM, Aitken PM, Best JD, Alford FP (1990) Effects of prolonged pulsatile hyperinsulinemia in humans. Enhancement of insulin sensitivity. Diabetes 39:501–507CrossRefPubMed Ward GM, Walters JM, Aitken PM, Best JD, Alford FP (1990) Effects of prolonged pulsatile hyperinsulinemia in humans. Enhancement of insulin sensitivity. Diabetes 39:501–507CrossRefPubMed
18.
19.
Zurück zum Zitat Bonner-Weir S (2000) Islet growth and development in the adult. J Mol Endocrinol 24:297–302CrossRefPubMed Bonner-Weir S (2000) Islet growth and development in the adult. J Mol Endocrinol 24:297–302CrossRefPubMed
20.
Zurück zum Zitat Verchere CB, D Alessio DA, Palmiter RD et al. (1996) Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide. Proc Natl Acad Sci USA 93:3492–3496CrossRefPubMedPubMedCentral Verchere CB, D Alessio DA, Palmiter RD et al. (1996) Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide. Proc Natl Acad Sci USA 93:3492–3496CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Kahn SE, Andrikopoulos S, Verchere CB (1999) Islet amyloid: a long-recognized but underappreciated pathological feature of type 2 diabetes. Diabetes 48:241–253CrossRefPubMed Kahn SE, Andrikopoulos S, Verchere CB (1999) Islet amyloid: a long-recognized but underappreciated pathological feature of type 2 diabetes. Diabetes 48:241–253CrossRefPubMed
22.
Zurück zum Zitat Janson J, Soeller WC, Roche PC et al. (1996) Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide. Proc Natl Acad Sci USA 93:7283–7288CrossRefPubMedPubMedCentral Janson J, Soeller WC, Roche PC et al. (1996) Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide. Proc Natl Acad Sci USA 93:7283–7288CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Westermark P (1996) Islet pathology of non-insulin-dependent diabetes mellitus (NIDDM). Diabet Med 13:S46–S48PubMed Westermark P (1996) Islet pathology of non-insulin-dependent diabetes mellitus (NIDDM). Diabet Med 13:S46–S48PubMed
24.
Zurück zum Zitat Eizirik DL, Mandrup-Poulsen T (2001) A choice of death—the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 44:2115–2133CrossRefPubMed Eizirik DL, Mandrup-Poulsen T (2001) A choice of death—the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 44:2115–2133CrossRefPubMed
25.
Zurück zum Zitat Corbett J, Serup P, Bonner Weir S, Nielsen JH (1997) Beta-cell ontogeny: growth and death. Diabetologia 40 [Suppl 3]:B27–B32 Corbett J, Serup P, Bonner Weir S, Nielsen JH (1997) Beta-cell ontogeny: growth and death. Diabetologia 40 [Suppl 3]:B27–B32
26.
Zurück zum Zitat Donath MY, Storling J, Maedler K, Mandrup-Poulsen T (2003) Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes. J Mol Med 81:455–470CrossRefPubMed Donath MY, Storling J, Maedler K, Mandrup-Poulsen T (2003) Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes. J Mol Med 81:455–470CrossRefPubMed
27.
Zurück zum Zitat Federici M, Hribal M, Perego L et al. (2001) High glucose causes apoptosis in cultured human pancreatic islets of Langerhans: a potential role for regulation of specific Bcl family genes toward an apoptotic cell death program. Diabetes 50:1290–1301CrossRefPubMed Federici M, Hribal M, Perego L et al. (2001) High glucose causes apoptosis in cultured human pancreatic islets of Langerhans: a potential role for regulation of specific Bcl family genes toward an apoptotic cell death program. Diabetes 50:1290–1301CrossRefPubMed
28.
Zurück zum Zitat Maedler K, Spinas GA, Lehmann R et al. (2001) Glucose induces beta-cell apoptosis via upregulation of the fas receptor in human islets. Diabetes 50:1683–1690CrossRefPubMed Maedler K, Spinas GA, Lehmann R et al. (2001) Glucose induces beta-cell apoptosis via upregulation of the fas receptor in human islets. Diabetes 50:1683–1690CrossRefPubMed
29.
Zurück zum Zitat Efanova IB, Zaitsev SV, Zhivotovsky B et al. (1998) Glucose and tolbutamide induce apoptosis in pancreatic beta-cells. A process dependent on intracellular Ca2+ concentration. JBC 273:33501–33507CrossRef Efanova IB, Zaitsev SV, Zhivotovsky B et al. (1998) Glucose and tolbutamide induce apoptosis in pancreatic beta-cells. A process dependent on intracellular Ca2+ concentration. JBC 273:33501–33507CrossRef
30.
Zurück zum Zitat Hoorens A, Van de Casteele M, Kloppel G, Pipeleers D (1996) Glucose promotes survival of rat pancreatic beta cells by activating synthesis of proteins which suppress a constitutive apoptotic program. JCI 98:1568–1574CrossRefPubMedPubMedCentral Hoorens A, Van de Casteele M, Kloppel G, Pipeleers D (1996) Glucose promotes survival of rat pancreatic beta cells by activating synthesis of proteins which suppress a constitutive apoptotic program. JCI 98:1568–1574CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Donath MY, Gross DJ, Cerasi E, Kaiser N (1999) Hyperglycemia-induced beta-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes 48:738–744CrossRefPubMed Donath MY, Gross DJ, Cerasi E, Kaiser N (1999) Hyperglycemia-induced beta-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes 48:738–744CrossRefPubMed
32.
Zurück zum Zitat Chick WL, Like AA (1970) Studies in the diabetic mutant mouse. 3. Physiological factors associated with alterations in beta cell proliferation. Diabetologia 6:243–251CrossRefPubMed Chick WL, Like AA (1970) Studies in the diabetic mutant mouse. 3. Physiological factors associated with alterations in beta cell proliferation. Diabetologia 6:243–251CrossRefPubMed
33.
Zurück zum Zitat Lipsett M, Finegood DT (2002) Beta-cell neogenesis during prolonged hyperglycemia in rats. Diabetes 51:1834–1841CrossRefPubMed Lipsett M, Finegood DT (2002) Beta-cell neogenesis during prolonged hyperglycemia in rats. Diabetes 51:1834–1841CrossRefPubMed
34.
Zurück zum Zitat Paris M, Bernard-Kargar C, Berthault MF, Bouwens L, Ktorza A (2003) Specific and combined effects of insulin and glucose on functional pancreatic beta-cell mass in vivo in adult rats. Endocrinology 144:2717–2727CrossRefPubMed Paris M, Bernard-Kargar C, Berthault MF, Bouwens L, Ktorza A (2003) Specific and combined effects of insulin and glucose on functional pancreatic beta-cell mass in vivo in adult rats. Endocrinology 144:2717–2727CrossRefPubMed
35.
Zurück zum Zitat Harding HP, Ron D (2002) Endoplasmic reticulum stress and the development of diabetes: a review. Diabetes 51:S455–S461CrossRefPubMed Harding HP, Ron D (2002) Endoplasmic reticulum stress and the development of diabetes: a review. Diabetes 51:S455–S461CrossRefPubMed
36.
Zurück zum Zitat Araki E, Oyadomari S, Mori M (2003) Endoplasmic reticulum stress and diabetes mellitus. Intern Med 42:7–14CrossRefPubMed Araki E, Oyadomari S, Mori M (2003) Endoplasmic reticulum stress and diabetes mellitus. Intern Med 42:7–14CrossRefPubMed
37.
Zurück zum Zitat Izumi T, Yokota-Hashimoto H, Zhao S, Wang J, Halban PA, Takeuchi T (2003) Dominant negative pathogenesis by mutant proinsulin in the akita diabetic mouse. Diabetes 52:409–416CrossRefPubMed Izumi T, Yokota-Hashimoto H, Zhao S, Wang J, Halban PA, Takeuchi T (2003) Dominant negative pathogenesis by mutant proinsulin in the akita diabetic mouse. Diabetes 52:409–416CrossRefPubMed
38.
Zurück zum Zitat Halban PA, Kahn SE, Lernmark A, Rhodes CJ (2001) Gene and cell-replacement therapy in the treatment of type 1 diabetes: how high must the standards be set? Diabetes 50:2181–2191CrossRefPubMed Halban PA, Kahn SE, Lernmark A, Rhodes CJ (2001) Gene and cell-replacement therapy in the treatment of type 1 diabetes: how high must the standards be set? Diabetes 50:2181–2191CrossRefPubMed
39.
Zurück zum Zitat Grill V, Bjorklund A (2001) Overstimulation and beta-cell function. Diabetes 50 [Suppl 1]:S122–124 Grill V, Bjorklund A (2001) Overstimulation and beta-cell function. Diabetes 50 [Suppl 1]:S122–124
40.
Zurück zum Zitat Ihara Y, Toyokuni S, Uchida K et al. (1999) Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. Diabetes 48:927–932CrossRefPubMed Ihara Y, Toyokuni S, Uchida K et al. (1999) Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. Diabetes 48:927–932CrossRefPubMed
41.
Zurück zum Zitat Laybutt DR, Kaneto H, Hasenkamp W et al. (2002) Increased expression of antioxidant and antiapoptotic genes in islets that may contribute to [beta]-cell survival during chronic hyperglycemia. Diabetes 51:413–423CrossRefPubMed Laybutt DR, Kaneto H, Hasenkamp W et al. (2002) Increased expression of antioxidant and antiapoptotic genes in islets that may contribute to [beta]-cell survival during chronic hyperglycemia. Diabetes 51:413–423CrossRefPubMed
42.
Zurück zum Zitat Maedler K, Sergeev P, Ris F et al. (2002) Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. JCI 110:851–860CrossRefPubMedPubMedCentral Maedler K, Sergeev P, Ris F et al. (2002) Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. JCI 110:851–860CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat Maedler K, Fontana A, Ris F et al. (2002) FLIP switches Fas-mediated glucose signaling in human pancreatic beta cells from apoptosis to cell replication. Proc Natl Acad Sci USA 99:8236–8241CrossRefPubMedPubMedCentral Maedler K, Fontana A, Ris F et al. (2002) FLIP switches Fas-mediated glucose signaling in human pancreatic beta cells from apoptosis to cell replication. Proc Natl Acad Sci USA 99:8236–8241CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Shimabukuro M, Zhou YT, Levi M, Unger RH (1998) Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci USA 95:2498–2502CrossRefPubMedPubMedCentral Shimabukuro M, Zhou YT, Levi M, Unger RH (1998) Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci USA 95:2498–2502CrossRefPubMedPubMedCentral
45.
Zurück zum Zitat Roehrich ME, Mooser V, Lenain V et al. (2003) Insulin-secreting beta-cell dysfunction induced by human lipoproteins. JBC 278:18368–18375CrossRef Roehrich ME, Mooser V, Lenain V et al. (2003) Insulin-secreting beta-cell dysfunction induced by human lipoproteins. JBC 278:18368–18375CrossRef
46.
Zurück zum Zitat Maedler K, Spinas GA, Dyntar D, Moritz W, Kaiser N, Donath MY (2001) Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function. Diabetes 50:69–76CrossRefPubMed Maedler K, Spinas GA, Dyntar D, Moritz W, Kaiser N, Donath MY (2001) Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function. Diabetes 50:69–76CrossRefPubMed
47.
Zurück zum Zitat Unger RH, Orci L (2002) Lipoapoptosis: its mechanism and its diseases. Biochim Biophys Acta 1585:202–212CrossRefPubMed Unger RH, Orci L (2002) Lipoapoptosis: its mechanism and its diseases. Biochim Biophys Acta 1585:202–212CrossRefPubMed
48.
Zurück zum Zitat Poitout V, Robertson RP (2002) Minireview: Secondary beta-Cell Failure in Type 2 Diabetes-A Convergence of Glucotoxicity and Lipotoxicity. Endocrinology 143:339–342 Poitout V, Robertson RP (2002) Minireview: Secondary beta-Cell Failure in Type 2 Diabetes-A Convergence of Glucotoxicity and Lipotoxicity. Endocrinology 143:339–342
49.
Zurück zum Zitat El-Assaad W, Buteau J, Peyot ML et al. (2003) Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death. Endocrinology 144:4154–4163CrossRefPubMed El-Assaad W, Buteau J, Peyot ML et al. (2003) Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death. Endocrinology 144:4154–4163CrossRefPubMed
50.
Zurück zum Zitat Roduit R, Thorens B (1997) Inhibition of glucose-induced insulin secretion by long-term preexposure of pancreatic islets to leptin. FEBS Lett 415:179–182CrossRefPubMed Roduit R, Thorens B (1997) Inhibition of glucose-induced insulin secretion by long-term preexposure of pancreatic islets to leptin. FEBS Lett 415:179–182CrossRefPubMed
51.
Zurück zum Zitat Kieffer TJ, Habener JF (2000) The adipoinsular axis: effects of leptin on pancreatic beta-cells. Am J Physiol Endocrinol Metab 278:E1–E14PubMed Kieffer TJ, Habener JF (2000) The adipoinsular axis: effects of leptin on pancreatic beta-cells. Am J Physiol Endocrinol Metab 278:E1–E14PubMed
52.
Zurück zum Zitat Shimabukuro M, Wang MY, Zhou YT, Newgard CB, Unger RH (1998) Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression. Proc Natl Acad Sci USA 95:9558–9561CrossRefPubMedPubMedCentral Shimabukuro M, Wang MY, Zhou YT, Newgard CB, Unger RH (1998) Protection against lipoapoptosis of beta cells through leptin-dependent maintenance of Bcl-2 expression. Proc Natl Acad Sci USA 95:9558–9561CrossRefPubMedPubMedCentral
53.
Zurück zum Zitat Kendall DM, Sutherland DE, Najarian JS, Goetz FC, Robertson RP (1990) Effects of hemipancreatectomy on insulin secretion and glucose tolerance in healthy humans. N Engl J Med 322:898–903CrossRefPubMed Kendall DM, Sutherland DE, Najarian JS, Goetz FC, Robertson RP (1990) Effects of hemipancreatectomy on insulin secretion and glucose tolerance in healthy humans. N Engl J Med 322:898–903CrossRefPubMed
54.
Zurück zum Zitat Bonner-Weir S, Trent DF, Weir GC (1983) Partial pancreatectomy in the rat and subsequent defect in glucose-induced insulin release. J Clin Invest 71:1544–1553CrossRefPubMedPubMedCentral Bonner-Weir S, Trent DF, Weir GC (1983) Partial pancreatectomy in the rat and subsequent defect in glucose-induced insulin release. J Clin Invest 71:1544–1553CrossRefPubMedPubMedCentral
55.
Zurück zum Zitat Weir GC, Leahy JL, Bonner-Weir S (1986) Experimental reduction of B-cell mass: implications for the pathogenesis of diabetes. Diabetes Metab Rev 2:125–161CrossRefPubMed Weir GC, Leahy JL, Bonner-Weir S (1986) Experimental reduction of B-cell mass: implications for the pathogenesis of diabetes. Diabetes Metab Rev 2:125–161CrossRefPubMed
56.
Zurück zum Zitat Kjems LL, Kirby BM, Welsh EM et al. (2001) Decrease in beta-cell mass leads to impaired pulsatile insulin secretion, reduced postprandial hepatic insulin clearance, and relative hyperglucagonemia in the minipig. Diabetes 50:2001–2012CrossRefPubMed Kjems LL, Kirby BM, Welsh EM et al. (2001) Decrease in beta-cell mass leads to impaired pulsatile insulin secretion, reduced postprandial hepatic insulin clearance, and relative hyperglucagonemia in the minipig. Diabetes 50:2001–2012CrossRefPubMed
57.
Zurück zum Zitat Kaiser N, Corcos AP, Sarel I, Cerasi E (1991) Monolayer culture of adult rat pancreatic islets on extracellular matrix: modulation of B-cell function by chronic exposure to high glucose. Endocrinology 129:2067–2076CrossRefPubMed Kaiser N, Corcos AP, Sarel I, Cerasi E (1991) Monolayer culture of adult rat pancreatic islets on extracellular matrix: modulation of B-cell function by chronic exposure to high glucose. Endocrinology 129:2067–2076CrossRefPubMed
58.
Zurück zum Zitat Eizirik DL, Korbutt GS, Hellerstrom C (1992) Prolonged exposure of human pancreatic islets to high glucose concentrations in vitro impairs the beta-cell function. J Clin Invest 90:1263–1268CrossRefPubMedPubMedCentral Eizirik DL, Korbutt GS, Hellerstrom C (1992) Prolonged exposure of human pancreatic islets to high glucose concentrations in vitro impairs the beta-cell function. J Clin Invest 90:1263–1268CrossRefPubMedPubMedCentral
59.
Zurück zum Zitat Leahy JL, Cooper HE, Deal DA, Weir GC (1986) Chronic hyperglycemia is associated with impaired glucose influence on insulin secretion. A study in normal rats using chronic in vivo glucose infusions. J Clin Invest 77:908–915CrossRefPubMedPubMedCentral Leahy JL, Cooper HE, Deal DA, Weir GC (1986) Chronic hyperglycemia is associated with impaired glucose influence on insulin secretion. A study in normal rats using chronic in vivo glucose infusions. J Clin Invest 77:908–915CrossRefPubMedPubMedCentral
60.
Zurück zum Zitat UK Prospective Diabetes Study Group (1995) UK prospective diabetes study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes 44:1249–1258CrossRef UK Prospective Diabetes Study Group (1995) UK prospective diabetes study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes 44:1249–1258CrossRef
61.
Zurück zum Zitat Leahy JL, Bonner-Weir S, Weir BC (1988) Minimal chronic hyperglycemia is a critical determinant of impaired insulin secretion after an incomplete pancreatectomy. J Clin Invest 81:1407–1414CrossRefPubMedPubMedCentral Leahy JL, Bonner-Weir S, Weir BC (1988) Minimal chronic hyperglycemia is a critical determinant of impaired insulin secretion after an incomplete pancreatectomy. J Clin Invest 81:1407–1414CrossRefPubMedPubMedCentral
62.
Zurück zum Zitat Kahn SE, Bergman RN, Schwartz MW, Taborsky GJ Jr, Porte D Jr (1992) Short-term hyperglycemia and hyperinsulinemia improve insulin action but do not alter glucose action in normal humans. Am J Physiol 262:E518–523PubMed Kahn SE, Bergman RN, Schwartz MW, Taborsky GJ Jr, Porte D Jr (1992) Short-term hyperglycemia and hyperinsulinemia improve insulin action but do not alter glucose action in normal humans. Am J Physiol 262:E518–523PubMed
63.
Zurück zum Zitat Glaser B, Cerasi E (1999) Early intensive insulin treatment for induction of long-term glycaemic control in type 2 diabetes. Diabetes Obes Metab 1:67–74CrossRefPubMed Glaser B, Cerasi E (1999) Early intensive insulin treatment for induction of long-term glycaemic control in type 2 diabetes. Diabetes Obes Metab 1:67–74CrossRefPubMed
64.
Zurück zum Zitat Polyzogopoulou EV, Kalfarentzos F, Vagenakis AG, Alexandrides TK (2003) Restoration of euglycemia and normal acute insulin response to glucose in obese subjects with type 2 diabetes following bariatric surgery. Diabetes 52:1098–1103CrossRefPubMed Polyzogopoulou EV, Kalfarentzos F, Vagenakis AG, Alexandrides TK (2003) Restoration of euglycemia and normal acute insulin response to glucose in obese subjects with type 2 diabetes following bariatric surgery. Diabetes 52:1098–1103CrossRefPubMed
65.
Zurück zum Zitat Li Y, Hansotia T, Yusta B, Ris F, Halban PA, Drucker DJ (2003) Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. JBC 278:471–478CrossRef Li Y, Hansotia T, Yusta B, Ris F, Halban PA, Drucker DJ (2003) Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. JBC 278:471–478CrossRef
66.
Zurück zum Zitat Drucker DJ (2003) Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol Endocrinol 17:161–171CrossRefPubMed Drucker DJ (2003) Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis. Mol Endocrinol 17:161–171CrossRefPubMed
67.
Zurück zum Zitat Greenwood RH, Mahler RF, Hales CN (1976) Improvement in insulin secretion in diabetes after diazoxide. Lancet 1:444–447CrossRefPubMed Greenwood RH, Mahler RF, Hales CN (1976) Improvement in insulin secretion in diabetes after diazoxide. Lancet 1:444–447CrossRefPubMed
68.
Zurück zum Zitat Bjork E, Berne C, Karlsson FA (1998) Induction of beta-cell rest in type 1 diabetes. Studies on the effects of octreotide and diazoxide. Diabetes Care 21:427–430CrossRefPubMed Bjork E, Berne C, Karlsson FA (1998) Induction of beta-cell rest in type 1 diabetes. Studies on the effects of octreotide and diazoxide. Diabetes Care 21:427–430CrossRefPubMed
69.
Zurück zum Zitat Guldstrand M, Grill V, Bjorklund A, Lins PE, Adamson U (2002) Improved beta cell function after short-term treatment with diazoxide in obese subjects with type 2 diabetes. Diabetes Metab 28:448–456PubMed Guldstrand M, Grill V, Bjorklund A, Lins PE, Adamson U (2002) Improved beta cell function after short-term treatment with diazoxide in obese subjects with type 2 diabetes. Diabetes Metab 28:448–456PubMed
70.
Zurück zum Zitat Report of the expert committee on the diagnosis and classification of diabetes mellitus (2003) Diabetes Care 26 [Suppl 1]:S5–S20 Report of the expert committee on the diagnosis and classification of diabetes mellitus (2003) Diabetes Care 26 [Suppl 1]:S5–S20
71.
Zurück zum Zitat Pietropaolo M, Barinas-Mitchell E, Pietropaolo SL, Kuller LH, Trucco M (2000) Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes. Diabetes 49:32–38CrossRefPubMed Pietropaolo M, Barinas-Mitchell E, Pietropaolo SL, Kuller LH, Trucco M (2000) Evidence of islet cell autoimmunity in elderly patients with type 2 diabetes. Diabetes 49:32–38CrossRefPubMed
72.
Zurück zum Zitat Hypponen E, Virtanen SM, Kenward MG, Knip M, Akerblom HK (2000) Obesity, increased linear growth, and risk of type 1 diabetes in children. Diabetes Care 23:1755–1760CrossRefPubMed Hypponen E, Virtanen SM, Kenward MG, Knip M, Akerblom HK (2000) Obesity, increased linear growth, and risk of type 1 diabetes in children. Diabetes Care 23:1755–1760CrossRefPubMed
73.
Zurück zum Zitat Kibirige M, Metcalf B, Renuka R, Wilkin TJ (2003) Testing the accelerator hypothesis: the relationship between body mass and age at diagnosis of type 1 diabetes. Diabetes Care 26:2865–2870CrossRefPubMed Kibirige M, Metcalf B, Renuka R, Wilkin TJ (2003) Testing the accelerator hypothesis: the relationship between body mass and age at diagnosis of type 1 diabetes. Diabetes Care 26:2865–2870CrossRefPubMed
74.
Zurück zum Zitat Libman IM, Pietropaolo M, Arslanian SA, LaPorte RE, Becker DJ (2003) Changing prevalence of overweight children and adolescents at onset of insulin-treated diabetes. Diabetes Care 26:2871–2875CrossRefPubMed Libman IM, Pietropaolo M, Arslanian SA, LaPorte RE, Becker DJ (2003) Changing prevalence of overweight children and adolescents at onset of insulin-treated diabetes. Diabetes Care 26:2871–2875CrossRefPubMed
75.
Zurück zum Zitat Syed MA, Barinas-Mitchell E, Pietropaolo SL et al. (2002) Is type 2 diabetes a chronic inflammatory/autoimmune disease? Diabetes Nutr Metab 15:68–83.PubMed Syed MA, Barinas-Mitchell E, Pietropaolo SL et al. (2002) Is type 2 diabetes a chronic inflammatory/autoimmune disease? Diabetes Nutr Metab 15:68–83.PubMed
76.
Zurück zum Zitat Pickup JC, Crook MA (1998) Is type II diabetes mellitus a disease of the innate immune system? Diabetologia 41:1241–1248CrossRefPubMed Pickup JC, Crook MA (1998) Is type II diabetes mellitus a disease of the innate immune system? Diabetologia 41:1241–1248CrossRefPubMed
77.
Zurück zum Zitat Spranger J, Kroke A, Mohlig M et al. (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52:812–817CrossRefPubMed Spranger J, Kroke A, Mohlig M et al. (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52:812–817CrossRefPubMed
78.
Zurück zum Zitat Bellone M, Iezzi G, Rovere P et al. (1997) Processing of engulfed apoptotic bodies yields T cell epitopes. J Immunol 159:5391–5399PubMed Bellone M, Iezzi G, Rovere P et al. (1997) Processing of engulfed apoptotic bodies yields T cell epitopes. J Immunol 159:5391–5399PubMed
79.
Zurück zum Zitat O’Brien BA, Harmon BV, Cameron DP, Allan DJ (1997) Apoptosis is the mode of beta-cell death responsible for the development of IDDM in the nonobese diabetic (NOD) mouse. Diabetes 46:750–757CrossRefPubMed O’Brien BA, Harmon BV, Cameron DP, Allan DJ (1997) Apoptosis is the mode of beta-cell death responsible for the development of IDDM in the nonobese diabetic (NOD) mouse. Diabetes 46:750–757CrossRefPubMed
81.
Zurück zum Zitat Wilkin TJ (2001) The accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes. Diabetologia 44:914–922CrossRefPubMed Wilkin TJ (2001) The accelerator hypothesis: weight gain as the missing link between Type I and Type II diabetes. Diabetologia 44:914–922CrossRefPubMed
82.
Zurück zum Zitat Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (1997) Diabetes Care 20:1183–1197CrossRef Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (1997) Diabetes Care 20:1183–1197CrossRef
83.
Zurück zum Zitat Diabetes Prevention Program (DPP) Research Group (2002) The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care 25:2165–2171CrossRef Diabetes Prevention Program (DPP) Research Group (2002) The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care 25:2165–2171CrossRef
84.
Zurück zum Zitat Tuomilehto J, Lindstrom J, Eriksson JG et al. (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350CrossRefPubMed Tuomilehto J, Lindstrom J, Eriksson JG et al. (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350CrossRefPubMed
85.
Zurück zum Zitat Pan XR, Li GW, Hu YH et al. (1997) Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 20:537–544CrossRefPubMed Pan XR, Li GW, Hu YH et al. (1997) Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 20:537–544CrossRefPubMed
86.
Zurück zum Zitat Maedler K, Bucher P, Berney T, Spinas GA, Carr RD, Donath MY (2003) Differential effects of repaglinide, nateglinide and glibenclamide on apoptosis in human beta cells in vitro. Diabetologia 46 [Suppl 2]:A187 (Abstract) Maedler K, Bucher P, Berney T, Spinas GA, Carr RD, Donath MY (2003) Differential effects of repaglinide, nateglinide and glibenclamide on apoptosis in human beta cells in vitro. Diabetologia 46 [Suppl 2]:A187 (Abstract)
87.
Zurück zum Zitat Alvarsson M, Sundkvist G, Lager I et al. (2003) Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients. Diabetes Care 26:2231–2237CrossRefPubMed Alvarsson M, Sundkvist G, Lager I et al. (2003) Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients. Diabetes Care 26:2231–2237CrossRefPubMed
Metadaten
Titel
Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications
verfasst von
M. Y. Donath
P. A. Halban
Publikationsdatum
01.03.2004
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 3/2004
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1336-4

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