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Pathophysiologie des Diabetes mellitus Typ2

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Klinische Diabetologie
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Zusammenfassung

Der Diabetes mellitus Typ 2 wird als ein heterogenes, nicht autoimmunbedingtes, multigenetisches Krankheitsbild definiert, das keine exogenen Insulingaben erfordert, um eine Ketoazidose zu vermeiden (National Diabetes Data Group 1979). In dieser Ausschlussdefinition spiegelt sich die Tatsache wider, dass es bis heute — ungeachtet einer Vielzahl von Einzelfakten — kein zusammenhängendes allgemeingültiges Krankheitskonzept für den Diabetes mellitus Typ 2 gibt.

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Literatur

  • Aizawa T, Komatsu M, Asanuma N, Sato Y, Sharp GW (1998) Glucose action „beyond ionic events“ in the pancreatic beta cell. Trends Pharmacol Sci 19: 496–499

    Article  PubMed  CAS  Google Scholar 

  • Alcolado JC, Baroni MG, Li SR (1991) Association between a restriction fragment length polymorphism at the liver/islet cell (GluT 2) glucose transporter and familial type 2 (non-insulindependent) diabetes mellitus. Diabetologia 34: 734–736

    Article  PubMed  CAS  Google Scholar 

  • Anai M, Fonaki M, Ogihara T, Kanda A, Onishi Y, Sakoda H, Inukai K, Nawano M, Fukushima Y, Yazaki Y, Kikuchi M, Oka Y, Asano T (1999) Enhanced insulin-stimulated activation of phosphatidylinositol-3’-kinase in the liver of highfat-feed rats. Diabetes 48: 158–169

    Article  PubMed  CAS  Google Scholar 

  • Ashcroft SJ (1980) Glucoreceptor mechanisms and the control of insulin release and biosynthesis. Diabetologia 18: 5–15

    Article  PubMed  CAS  Google Scholar 

  • Barnett AH, Eff C, Leslie RD, Pyke DA (1981) Diabetes in identical twins. A study of zoo pairs. Diabetologia 20: 87–93

    Article  PubMed  CAS  Google Scholar 

  • Berson SA, Yalow RS (1970) Insulin antagonists and insulin resistance. In: Ellenberg M, Rifkin H (eds) Diabetes mellitus: theory and practice. McGraw-Hill, New York, pp 388–423

    Google Scholar 

  • Boden G (1999) Free fatty acids, insulin resistance, and type 2 diabetes. Proc Assoc Am Physicians 111: 241–248

    Article  PubMed  CAS  Google Scholar 

  • Bollheimer LC, Skelly RH, Chester MW, McGarry JD, Rhodes CJ (1998) Chronic exposure to free fatty acid reduces pancreatic beta cell insulin content by increasing basal insulin secretion that is not compensated for by a corresponding increase in proinsulin biosynthesis translation. J Clin Invest soi: 1094–1101

    Google Scholar 

  • Cerasi E (1995) Insulin deficiency and insulin resistance in the pathogenesis of NIDDM: is a divorce possible? Diabetologia 38: 992–997

    Article  PubMed  CAS  Google Scholar 

  • Clark A, Wells CA, Buley ID, Cruickshank JK, Vanhegan RI, Matthews DR, Cooper GJ, Holman RR, Turner RC (1988) Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes. Diabetes Res 9: 151–159

    PubMed  CAS  Google Scholar 

  • Cohen P (1999) The Croonian Lecture 1998. Identification of a protein kinase cascade of major importance in insulin signal transduction. Philos Trans R Soc Lond B Biol Sci 354: 485–495

    Article  PubMed  CAS  Google Scholar 

  • Consoli A, Nurjhan N, Capani F, Gerich J (1989) Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM. Diabetes 38: 550–557

    Article  PubMed  CAS  Google Scholar 

  • Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA (1995) Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378: 785–789

    Article  PubMed  CAS  Google Scholar 

  • DeFronzo RA (1988) Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37: 667–687

    PubMed  CAS  Google Scholar 

  • DeFronzo RA (1997) Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev 5: 877–894

    Google Scholar 

  • DeFronzo RA (1999) Pharmacologic therapy for type diabetes mellitus. Ann Intern Med 131: 281–303

    PubMed  CAS  Google Scholar 

  • Dent P Lavoinne A, Nakielny S, Caudwell FB, Watt P, Cohen P (1990) The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle. Nature 348: 302–308

    Article  PubMed  CAS  Google Scholar 

  • Felber JP, Vanotti A (1964) Effects of fat infusions on glucose tolerance and insulin plasma levels. Med Exp 10: 153–156

    PubMed  CAS  Google Scholar 

  • Froguel P, Zouali H, Vionnet N, Velho G, Vaxillaire M, Sun F, Lesage S, Stoffel M, Takeda J, Passa P, Permutt MA, Beckmann JS, Bell GI, Cohen D (1993) Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. N Engl J Med 328: 697–702

    Article  PubMed  CAS  Google Scholar 

  • Furukawa H, Carroll RJ, Swift HH, Steiner DF(1999) Longterm elevation of free fatty acids leads to delayed processing for proinsulin and prohormon convertases 2 and 3 pancreatic beta-cell line MIN6. Diabetes 48: 1395–1401

    Article  PubMed  CAS  Google Scholar 

  • Gembal M, Detimary P, Gilon P, Gao ZY, Henquin JC (1993) Mechanisms by which glucose can control insulin release independently from its action on adenosine triphosphate-sensitive K+ channels in mouse B cells. J Clin Invest 91: 871–880

    Article  PubMed  CAS  Google Scholar 

  • Granner D, Pilkis S (1990) The genes of hepatic glucose metabolism. J Biol Chem 265: 10173–10176

    PubMed  CAS  Google Scholar 

  • Grodsky GM (1989) A new phase of insulin secretion. How will it contribute to our understanding of beta-cell function? Diabetes 38: 673–678

    Article  PubMed  CAS  Google Scholar 

  • Halban PA, Irminger JC (1994) Sorting and processing of secretory proteins. Biochem J 299: 1–18

    PubMed  CAS  Google Scholar 

  • Hall RK, Granner DK (1999) Insulin regulates expression of metabolic genes through divergent signaling pathways. J Basic Clin Physiol Pharmacol 10: 119–133

    Article  PubMed  CAS  Google Scholar 

  • Harbeck MC, Louie DC, Howland J, Wolf BA, Rothenberg PL (1996) Expression of insulin receptor mRNA and insulin receptor substrate 1 in pancreatic islet beta-cells. Diabetes 45: 711–717

    Article  PubMed  CAS  Google Scholar 

  • Himsworth HP (1936) Diabetes mellitus: Its differentiation into insulin sensitive and insulin insensitive types. Lancet 1: 127–130

    Article  Google Scholar 

  • Homo-Delarche F (1997) Beta-cell behavior during the prediabetic stage. Part I. Beta-cell pathophysiology. Diabetes Me-tab 23: 473–505

    CAS  Google Scholar 

  • Hügl RS, White MF, Rhodes CJ (1998) Insuline-like growth factor I (IGF-I)-stimulated pancreatic beta-cell growth is glucose-dependent. Synergistic activation of insulin receptor substrate-mediated signal transduction pathways by glucose and IGF-I in INS-I cells. J Biol Chem 28: 17771–17779

    Article  Google Scholar 

  • Hunter SJ, Garvey WT (1998) Insulin action and insulin resistance: diseases involving defects in insulin receptors, signal transduction, and the glucose transport effector system. Am J Med l05: 331–345

    Article  PubMed  CAS  Google Scholar 

  • Janssen RC, Bogardus C, Takeda J, Knowler WC, Thompson DB (1994) Linkage analysis of acute insulin secretion with GLUT2 and glucokinase in Pima Indians and the identification of a missense mutation in GLUT2. Diabetes 43: 558–563

    Article  PubMed  CAS  Google Scholar 

  • Kahn BB (1998) Type 2 diabetes: when insulin secretion fails to compensate for insulin resistance. Cell 92: 593–596

    Article  PubMed  CAS  Google Scholar 

  • Kahn CR (1978) Insulin resistance, insulin insensitivity, and insulin unresponsiveness: a necessary distinction. Metabolism 27 Suppl 2: 1893–1902

    Google Scholar 

  • Kahn CR, Vicenct D, Doria A (1996) Genetics of non-insulindependent (type-II) diabetes mellitus. Annu Rev Med 47: 509–531

    Article  PubMed  CAS  Google Scholar 

  • Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR (1999) Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96: 329–339

    Article  PubMed  CAS  Google Scholar 

  • Lebovitz HE (1999) Insulin scretagogues: old and new. Diabetes Reviews 7: 139

    Google Scholar 

  • Liang Y, Matschinsky FM (1994) Mechanisms of action of non- glucose insulin secretagogues. Annu Rev Nutr 14: 59–81

    Article  PubMed  CAS  Google Scholar 

  • Lillioja S, Nyomba BL, Saad MF, Ferraro R, Castillo C, Bennett PH, Bogardus C (1990) Exaggerated early insulin release and insulin resistance resistance in a diabetic-prone population: a metabolic comparison of Pima Indians and Caucasians. J Clin Endocrinol Metab 73: 866–876

    Article  Google Scholar 

  • McGarry MC (1992) What if Minkowsky had been ageusic? An alternative angle to diabetes? Science 258: 766–774

    Article  PubMed  CAS  Google Scholar 

  • Milburn JL, Hirose H, Lee YH, Nagasawa Y, Ogawa A, Ohneda M, BeltandelRio H, Newgard CB, Johnson JH, Unger RH (1995) Pancreatic beta-cells in obesity: evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids. J Biol Chem 270: 1295–1299.

    Article  PubMed  CAS  Google Scholar 

  • National Diabetes Data Group (1979) Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: 1039–1057

    Google Scholar 

  • Newgard CB, McGarry JD (1995) Metabolic coupling factors in pancreatic beta-cell signal transduction. Annu Rev Biochem 64: 689–719

    Article  PubMed  CAS  Google Scholar 

  • Owerbach D, Bell GI, Rutter WJ, Shows TB (1980) The insulin gene is located on chromosome 11 in humans. Nature 186: 82–84

    Article  Google Scholar 

  • Patel P, Bell GI, Cook JT, Turner RC, Wainscoat JS (1991) Multiple restriction fragment length polymorphisms at the GLUT2 locus: GLUT2 haplotypes for genetic analysis of type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 34: 817–821

    Article  PubMed  CAS  Google Scholar 

  • Pedersen O (1999) Genetics of insulin resistance. Exp Clin Endocrinol Diabetes 107: 113–118

    Article  PubMed  CAS  Google Scholar 

  • Polonsky WH (1995) Lilly lecture 1994. The beta-cell in diabetes: from molecular genetics to clinical research. Diabetes 44: 705–717

    Article  PubMed  CAS  Google Scholar 

  • Prentki M, Corkey BE (1996) Are the beta-cell signaling molecules malonyl-CoA and cystolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM? Diabetes 45: 273–283

    Article  PubMed  CAS  Google Scholar 

  • Randle PJ (1998) Regulatory interactions between the lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev 14: 263–283

    Article  PubMed  CAS  Google Scholar 

  • Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty acid cycle: its role in insulin sensitivity an the metabolic disturbances of diabetes mellitus. Lancet 1: 785–789

    Article  PubMed  CAS  Google Scholar 

  • Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37: 1595–1607

    Article  PubMed  CAS  Google Scholar 

  • Reaven GM (1995) The forth musketeer–from Alexandre Dumas to Claude Bernard. Diabetologia 38: 3–13

    Article  PubMed  CAS  Google Scholar 

  • Reaven GM, Olefsky JM (1977) Relationship between heterogeneity of insulin responses and insulin resistance in normal subjects and patients with chemical diabetes. Diabetologia 13: 201–206

    Article  PubMed  CAS  Google Scholar 

  • Rebrin K, Steil GM, Getty L, Bergman RN (1995) Free fatty acid as a link in the regulation of hepatic glucose output by peripheral insulin. Diabetes 44: 1038–1045

    Article  PubMed  CAS  Google Scholar 

  • Rhodes CJ, Alarcon C (1994) What beta-cell defect could lead to hyperproinsulinemia in NIDDM? Some clues from recent advances made in understanding the proinsulin-processing mechanism. Diabetes 43: 511–517

    Article  PubMed  CAS  Google Scholar 

  • Sacks D, McDonald JM (1995) The pathogenesis of type II diabetes mellitus. A polygenic disease. Am J Clin Pathol 105: 149–156

    Google Scholar 

  • Saltiel AR (1996) Diverse signaling pathways in the cellular actions of insulin. Am J Physiol 270: E375 - E385

    PubMed  CAS  Google Scholar 

  • Seely BL, Olefsky JM (1993) Potential cellular and genetic mechanisms for insulin resistance in the common disorders of diabetes and obesity. Baillieres Endocrinol Metabol Vol: 187–245

    Google Scholar 

  • Shimada F, Makino H, Iwaoka H, Miyamoto S, Hashimoto N, Kanatsuka A, Bell GI, Yoshida S (1995) Identification of two novel amino acid polymorphisms in beta-cell/liver (GLUT2) glucose transporter in Japanese subjects. Diabetologia 38: 211–215

    Article  PubMed  CAS  Google Scholar 

  • Shulman GI (1999) Cellular mechanisms of insulin resistance in humans. Am J Cardiol 84: 3J - l0J

    Article  PubMed  CAS  Google Scholar 

  • Sjöholm A (1998) Aspects of novel sites of regulation of the insulin stimulus-secretion coupling in normal and diabetic pancreatic islets. Endocrine 9: 1–13

    Article  PubMed  Google Scholar 

  • Skelly RH, Bollheimer LC, Wicksteed BL, Corkey B, Rhodes CJ (1998) A distinct difference in the better body stimulus-response coupling pathways for regulating proinsulin biosynthesis and insulin secretion that lies at the level of requirement for fatty acyl moieties. Biochem J 331: 553–561

    PubMed  CAS  Google Scholar 

  • Stoffel M, Bell GI (1993) Characterization of a third simple tandem repeat polymorphism in the human glucokinase gene. Diabetologia 36: 170–171

    Article  PubMed  CAS  Google Scholar 

  • Swenne I (1992) Pancreatic beta-cell growth and diabetes mellitus. Diabetologia 35: 193–201

    Article  PubMed  CAS  Google Scholar 

  • Taylor SI (1992) Lilly Lecture. Molecular mechanisms of insulin resistance. Lessons from patients with mutations in the insulin-receptor gene. Diabetes 41: 1473–1490

    Article  PubMed  CAS  Google Scholar 

  • Taylor SI, Accili D, Imai Y (1994) Insulin resistance or insulin deficiency. Which is the primary cause of NIDDM? Diabetes 43: 735–740

    PubMed  CAS  Google Scholar 

  • Unger RH (1995) Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes 44: 863–870

    Article  PubMed  CAS  Google Scholar 

  • Verspohl EJ, Ammon HP (1980) Evidence for presence of insulin receptors in red islets of Langerhans. J Clin Invest 65: 1230–1237

    Article  PubMed  CAS  Google Scholar 

  • Waldhäusl W, Bratusch-Marrain P, Gasic S, Korn A, Nowotny P (1982) Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 23: 6–15

    Article  PubMed  Google Scholar 

  • White MF, Kahn CR (1994) The insulin signaling system. J Biol Chem 269: 1–4

    PubMed  CAS  Google Scholar 

  • Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, Bonner-Weir S, White MF (1998) Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391: 900–904

    Article  PubMed  CAS  Google Scholar 

  • Yalow RS, Berson SA (1960a) Immunoassay of plasma insulin in man. J Clin Invest 39: 1157

    Article  PubMed  CAS  Google Scholar 

  • Yalow RS, Berson SA (1960b) Plasma insulin concentrations in nondiabetic and early diabetic subjects. Diabetes 9: 254

    PubMed  CAS  Google Scholar 

  • Yoshida H, Ohagi S, Sanke T, Furuta H, Furuta M, Nanjo K (1995) Association of the prohormone convertase 2 gene (PCSK2) and chromosome 20 with NIDDM in Japanese subjects. Diabetes 44: 389–393

    Article  PubMed  CAS  Google Scholar 

  • Yoshioka N, Kuzuya T, Matsuda A, Taniguchi M, Iwamoto Y (1988) Serum proinsulin levels at fasting and after oral glucose load in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 31: 355–360

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Warren-Perry M, Sakura H, Adelman J, Stoffel M, Bell GI, Ashcroft FM, Turner RC (1995) No evidence for mutations in a putative beta-cell ATP-sensitive K+ channel subunit in MODY, NIDDM, or GDM. Diabetes 44: 597–600

    Article  PubMed  CAS  Google Scholar 

  • Zisman A, Peroni OD, Abel ED, Michael MD, Mauvais-Jarvis F, Lowell BB, Wojtaszewski JFP, Hishman MF, Virkamaki A, Goodyear LJ, Kahn CR, Kahn BB (2000) Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nature Med 6: 924–928

    Article  PubMed  CAS  Google Scholar 

  • Zhou YP, Grill VE (1994) Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle. J Clin Invest 93: 870–876.

    Article  PubMed  CAS  Google Scholar 

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Palitzsch, KD., Bollheimer, C. (2001). Pathophysiologie des Diabetes mellitus Typ2. In: Böhm, B.O., Palitzsch, KD., Rosak, C., Spinas, G.A. (eds) Klinische Diabetologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59539-4_4

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