Mitochondrien als Kraftwerk der β-Zelle

详细信息    查看全文

• 作者：Prof. S. Baltrusch ; F. Reinhardt ; M. Tiedge
• 关键词：Typ ; 2 ; Diabetes ; Insulin ; Energiemetabolismus ; Mitochondriale Dysfunktion ; Apoptose ; Type 2 diabetes mellitus ; Insulin ; Energy metabolism ; Mitochondrial dysfunction ; Apoptosis
• 刊名：Der Diabetologe
• 出版年：2015
• 出版时间：May 2015
• 年：2015
• 卷：11
• 期：3
• 页码：231-242
• 全文大小：754 KB
• 参考文献：1.Kahn SE, Cooper ME, Del Prato S (2014) Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 383:1068-083View Article PubMed Central PubMed
  2.Haataja L, Gurlo T, Huang CJ et al (2008) Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis. Endocr Rev 29:303-16View Article PubMed Central PubMed
  3.Florez JC, Hirschhorn J, Altshuler D (2003) The inherited basis of diabetes mellitus: implications for the genetic analysis of complex traits. Annu Rev Genomics Hum Genet 4:257-91View Article PubMed
  4.Drong AW, Lindgren CM, McCarthy MI (2012) The genetic and epigenetic basis of type 2 diabetes and obesity. Clin Pharmacol Ther 92:707-15View Article PubMed
  5.Meigs JB, Cupples LA, Wilson PW (2000) Parental transmission of type 2 diabetes: the Framingham Offspring Study. Diabetes 49:2201-207View Article PubMed
  6.Pal A, McCarthy MI (2013) The genetics of type 2 diabetes and its clinical relevance. Clin Genet 83:297-06View Article PubMed
  7.Donath MY, Schumann DM, Faulenbach M et al (2008) Islet inflammation in type 2 diabetes: from metabolic stress to therapy. Diabetes Care 31(Suppl 2):161-64View Article
  8.Tiedge M, Lortz S, Drinkgern J et al (1997) Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 46:1733-742View Article PubMed
  9.Eizirik DL, Cardozo AK, Cnop M (2008) The role for endoplasmic reticulum stress in diabetes mellitus. Endocr Rev 29:42-1View Article PubMed
  10.Jin W, Patti ME (2009) Genetic determinants and molecular pathways in the pathogenesis of type 2 diabetes. Clin Sci 116:99-11View Article PubMed
  11.Gallagher EJ, Leroith D, Karnieli E (2010) Insulin resistance in obesity as the underlying cause for the metabolic syndrome. Mt Sinai J Med 77:511-23View Article PubMed
  12.Jung HS, Lee MS (2010) Role of autophagy in diabetes and mitochondria. Ann N Y Acad Sci 1201:79-3View Article PubMed
  13.Nolan CJ, Madiraju MS, Delghingaro-Augusto V et al (2006) Fatty acid signaling in the beta-cell and insulin secretion. Diabetes 55(Suppl 2):16-3View Article
  14.Poitout V, Robertson RP (2008) Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev 29:351-66View Article PubMed Central PubMed
  15.Newsholme P, Haber EP, Hirabara SM et al (2007) Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. J Physiol 583:9-4View Article PubMed Central PubMed
  16.Takahashi HK, Santos LR, Roma LP et al (2014) Acute nutrient regulation of the mitochondrial glutathione redox state in pancreatic beta-cells. Biochem J 460:411-23View Article PubMed
  17.El-Assaad W, Joly E, Barbeau A et al (2010) Glucolipotoxicity alters lipid partitioning and causes mitochondrial dysfunction, cholesterol, and ceramide deposition and reactive oxygen species production in INS832/13 ss-cells. Endocrinology 151:3061-073View Article PubMed
  18.Lupi R, Dotta F, Marselli L et al (2002) Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes 51:1437-442View Article PubMed
  19.Baltrusch S, Tiedge M (2006) Glucokinase regulatory network in pancreatic beta-cells and liver. Diabetes 55(Suppl 2):55-4View Article
  20.Schuit F, De Vos A, Farfari S et al (1997) Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in beta cells. J Biol Chem 272:18572-8579View Article PubMed
  21.Prentki M, Tornheim K, Corkey BE (1997) Signal transduction mechanisms in nutrient-induced insulin secretion. Diabetologia 40(Suppl 2):32-1View Article
  22.Maechler P (2002) Mitochondria as the conductor of metabolic signals for insulin exocytosis in pancreatic beta-cells. Cell Mol Life Sci 59:1803-818View Article PubMed
  23.Wiederkehr A, Wollheim CB (2012) Mitochondrial signals drive insulin secretion in the pancreatic β-cell. Mol Cell Endocrinol 353:128-37View Article PubMed
  24.Henquin JC (2009) Regulation of insulin secretion: a matter of phase control and amplitude modulation. Diabetologia 52:739-51View Article PubMed
  25.Kim JW, Yoon KH (2011) Glucolipotoxicity in pancreatic beta-cells. Diabetes Metab J 35:444-50View Article PubMed Central PubMed
  26.Poitout V, Amyot J, Semache M et al (2010) Glucolipotoxicity of the pancreatic beta cell. Biochim Biophys Acta 1801:289-98View Article PubMed Central PubMed
  27.Chawla A, Nguyen KD, Goh YP (2011) Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol 11:738-49View Article PubMed Central PubMed
  28.Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415-45View Article PubMed
  29.Johnson DC, Dean DR, Smith AD et al (2005) Structure, function, and formation of biologi
• 作者单位：Prof. S. Baltrusch (1)
  F. Reinhardt (1)
  M. Tiedge (1)
  
  1. Institut für Medizinische Biochemie und Molekularbiologie, Universit?tsmedizin Rostock, Schillingallee 70, 18057, Rostock, Deutschland
  
• 刊物主题：Diabetes; General Practice / Family Medicine; Internal Medicine; Angiology; Endocrinology; Metabolic Diseases;
• 出版者：Springer Berlin Heidelberg
• ISSN：1860-9724

文摘

Glucose intolerance is the major cause of type 2 diabetes mellitus (T2DM). In addition to peripheral insulin resistance, pancreatic beta cell dysfunction with reduced insulin secretion contributes to T2DM manifestation. The glucose sensor enzyme glucokinase is the key regulator in beta cells coupling an increase in blood glucose to insulin secretion. This demand-based insulin secretion is important for blood glucose homeostasis and cellular energy metabolism despite changing substrate availability from carbohydrates, fat and proteins. Supernutrition induces an imbalance in this control loop. Mitochondria are the pivotal organelles of cellular energy. The mitochondrial morphology is crucial to maintain their function and is by no means fixed but highly dynamic. Mitochondria form a tubular network in β-cells, which frequently undergoes fusion and fission events. Hyperglycemia and hyperlipidemia promote maladjustment of the mitochondrial network, thus contributing to mitochondrial dysfunction and promoting T2DM.