High-Fat Diets and β-Cell Dysfunction: Molecular Aspects

Molecular Nutrition and Diabetes: A Volume in the Molecular Nutrition Series

Volumn , Issue , 2016, Pages 115-130

  Collares Buzato, Carla Beatriz ^a  

^a UNIVERSITY OF CAMPINAS   (Brazil)

Author keywords

Compensatory cell response; High fat diets; Insulin biosynthesis; Insulin secretion; Obesity; Type 2 diabetes; cell apoptosis; cell dysfunction

Indexed keywords

EID: 84967261240     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-0-12-801585-8.00010-5     Document Type: Chapter

References (133)

1. Tripathy D., Chavez A.O. Defects in insulin secretion and action in the pathogenesis of type 2 diabetes mellitus. Curr Diab Rep 2010, 10:184-191.
2. Ferrannini E., Gastaldelli A., Iozzo P. Pathophysiology of prediabetes. Med Clin N Am 2011, 95:327-339.
3. Ashcroft F.M., Rorsman P. Diabetes mellitus and the β-cell: the last ten years. Cell 2012, 148:1160-1171.
4. Wu Y., Ding Y., Tanaka Y., Zhang W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int J Med Sci 2014, 11:1185-1200.
5. Sone H., Kagawa Y. Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice. Diabetologia 2005, 48:58-67.
6. Kahn S.E., Hull R.L., Utzschneider K.M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006, 14:840-846.
7. Prentki M., Nolan C.J. Islet beta cell failure in type 2 diabetes. J Clin Invest 2006, 116:1802-1812.
8. Hameed I., Masoodi S.R., Mir S.A., Nabi M., Ghazanfar K., Ganai B.A. Type 2 diabetes mellitus: from a metabolic disorder to an inflammatory condition. World J Diabetes 2015, 6(4):598-612.
9. Saisho Y. β-Cell dysfunction: its critical role in prevention and management of type 2 diabetes. World J Diabetes 2015, 6(1):109-124.
10. Lee Y.C., Nielsen J.H. Regulation of beta cell replication. Mol Cell Endocrinol 2009, 29:18-27.
11. Li Q., Lai Z.-Q. Recent progress in studies of factors that elicit pancreatic β-cell expansion. Protein Cell 2015, 6(2):81-87.
12. Hollingdal M., Juhl C.B., Pincus S.M., et al. Failure of physiological plasma glucose excursions to entrain high-frequency pulsatile insulin secretion in type 2 diabetes. Diabetes 2000, 49:1334-1340.
13. Shoelson S.E., Lee J., Goldfine A.B. Inflammation and insulin resistance. J Clin Invest 2006, 116:1793-1801.
14. Inadera H. Developmental origins of obesity and type 2 diabetes: molecular aspects and role of chemicals. Environ Health Prev Med 2013, 18:185-197.
15. Al-Goblan A.S., Al-Alfi M.A., Khan M.Z. Mechanism linking diabetes mellitus and obesity. Diabetes, Metab Syndr Obes 2014, 7:587-591.
16. Lai M., Chandrasekera P.C., Barnard N.D. You are what you eat, or are you? The challenges of translating high-fat-fed rodents to human obesity and diabetes. Nutr Diabetes 2014, 4:e135.
17. Surwit R.S., Kuhn C.M., Cochrane C., McCubbin J.A., Feinglos M.N. Diet-induced type II diabetes in C57BL/6J mice. Diabetes 1988, 37:1163-1167.
18. Winzell M.S., Ahrén B. The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 2003, 53:S215-S219.
19. Hatanaka M., Maier B., Sims E.K., et al. Palmitate induces mRNA translation and increases ER protein load in islet beta-cells via activation of the mammalian target of rapamycin pathway. Diabetes 2014, 63:3404-3415.
20. Oliveira R.B., Maschio D.A., Carvalho C.P., Collares-Buzato C.B. Influence of gender and time diet exposure on endocrine pancreas remodeling in response to high fat diet-induced metabolic disturbances in mice. Ann Anat 2015, 200:88-97.
21. Arner P., Rydén M. Fatty acids, obesity and insulin resistance. Obes Facts 2015, 8:147-155.
22. Ahren J., Ahren B., Wierup N. Increased β-cell volume in mice fed a high-fat diet A dynamic study over 12months. Islets 2010, 6:353-356.
23. Nagao M., Asai A., Inaba W., et al. Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance. PLoS One 2014, 9(1):e84725.
24. Oliveira R.B., Carvalho C.P., Polo C.C., Dorighello G., Boschero A.C., d Oliveira H.C., et al. Impaired compensatory beta-cell function and growth in response to high-fat diet in LDL receptor knockout mice. Int J Exp Pathol 2014, 95:296-308.
25. In't Veld P., Marichal M. Microscopic anatomy of the human islet of Langerhans. Advances in experimental medicine and biology 2011, vol. 654:1-19. M.S. Islam (Ed.).
26. Carvalho C.P., Martins J.C., Da Cunha D.A., Boschero A.C., Collares-Buzato C.B. Histomorphology and ultrastructure of pancreatic islet tissue during in vivo maturation of rat pancreas. Ann Anat 2006, 188:221-234.
27. Kim A., Miller K., Junghyo J., Kilimnik G., Wojcik P., Hara M. Islet architecture: a comparative study. Islets 2009, 1(2):129-136.
28. Bosco D., Armanet M., Morel P., et al. Unique arrangement of α and β-cells in human islets of Langerhans. Diabetes 2010, 59:1202-1210.
29. Jain R., Lammert E. Cell-cell interactions in the endocrine pancreas. Diabetes Obes Metab 2009, 11(Suppl. 4):159-167.
30. Carvalho C.P., Oliveira R.B., Santos-Silva J.C., Boschero A.C., Meda P., Collares-Buzato C.B. Impaired β-cellβ-cell coupling mediated by Cx36 gap junctions in prediabetic mice. Am J Physiol Endocrinol Metab 2012, 303:144-145.
31. Santos-Silva J.C., Carvalho C.P., de Oliveira R.B., Boschero A.C., Collares-Buzato C.B. Cell-to-cell contact dependence and junctional protein content are correlated with in vivo maturation of pancreatic beta cells. Can J Physiol Pharmacol 2012, 90:837-850.
32. Fu Z., Gilbert E.R., Liu D. Regulation of insulin synthesis and secretion and pancreatic beta-cell dysfunction in diabetes. Curr Diabetes Rev 2013, 9(1):25-53.
33. Suckale J., Solimena M. Pancreas islets in metabolic signaling-focus on the beta-cell. Front Biosci 2008, 13:7156-7171.
34. McCulloch L.J., van de Bunt M., Braun M., Frayn K.N., Clark A., Gloyn A.L. GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta cells: implications for understanding genetic association signals at this locus. Mol Genet Metab 2011, 104(4):648-653.
35. MacDonald P.E. Signal integration at the level of ion channel and exocytotic function in pancreatic β-cell. Am J Physiol Endocrinol Metab 2011, 301:E1065-E1069.
36. Wang Z., Thurmond D.C. Mechanisms of biphasic insulin-granule exocytosis - roles of the cytoskeleton, small GTPases and SNARE proteins. J Cell Sci 2009, 122:893-903.
37. Schuit F.C., In't Veld P.A., Pipeleers D.G. Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of pancreatic beta cells (protein synthesis/beta cell heterogeneity/insulin). Proc Natl Acad Sci USA 1988, 85:3865-3869.
38. Cnop M., Igoillo-Esteve M., Cunha D.A., Ladriere L., Eizirik D.L. An update on lipotoxic endoplasmic reticulum stress in pancreatic β-cells. Biochem Soc Trans 2008, 36:909-915.
39. Papa F.R. Endoplasmic reticulum stress, pancreatic β-cell degeneration, and diabetes. Cold Spring Harb Perspect Med 2012, 2:a007666.
40. Vetere A., Choudhary A., Wagner B.K. Targeting the pancreatic β-cell to treat diabetes. Nat Rev Drug Discov 2014, 13(4):278-289.
41. Cernea S., Dobreanu M. Diabetes and beta cell function: from mechanisms to evaluation and clinical implications. Biochem Medica 2013, 23(3):266-280.
42. Liu J., Li J., Li W.-J., Wang C.-M. The role of uncoupling proteins in diabetes mellitus. J Diabetes Res 2013, 2013:585897-585904.
43. Bosco D., Haefliger J.-A., Meda P. Connexins: key mediators of endocrine function. Physiol Rev 2011, 91:1393-1445.
44. Carvalho C.P.F., Barbosa H.C.L., Britan A., Boschero A.C., Meda P., Collares-Buzato C.B. Beta cell coupling and connexin expression change during the functional maturation of rat pancreatic islets. Diabetologia 2010, 53:1428-1437.
45. Collares-Buzato C.B., Carvalho C.P.F., Furtado A.G., Boschero A.C. Upregulation of the expression of tight and adherens junction-associated proteins during maturation of neonatal pancreatic islets in vitro. J Mol Histol 2004, 35:811-822.
46. De Kort S., Keszthelyi D., Masclee A.A.M. Etiology and pathophysiology - leaky gut and diabetes mellitus: what is the link?. Obes Rev 2011, 12:449-458.
47. Kanno A., Asahara S., Masuda K., et al. Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets. Biochem Biophys Res Commun 2015, 458:681-686.
48. Gonzalez A., Merino B., Marroquí L., et al. Insulin hypersecretion in islets from diet-induced hyperinsulinemic obese female mice is associated with several functional adaptations in individual β-cells. Endocrinology 2013, 154:3515-3524.
49. Fex M., Nitert M.D., Wierup N., Sundler F., Ling C., Mulder H. Enhanced mitochondrial metabolism may account for the adaptation to insulin resistance in islets from C57BL/6J mice fed a high-fat diet. Diabetologia 2007, 50:74-83.
50. Warnotte C., Gilon P., Nenquin M., Henquin J.C. Mechanisms of the stimulation of insulin release by saturated fatty acids. A study of palmitate effects in mouse beta-cells. Diabetes 1994, 43(5):703-711.
51. Tian Y., Corkey R.F., Yaney G.C., Goforth P.B., Satin L.S., Moitoso de Vargas L. Differential modulation of L-type calcium channel subunits by oleate. Am J Physiol Endocrinol Metab 2008, 294:E1178-E1186.
52. Montanya E. Insulin resistance compensation: not just a matter of beta-cells?. Diabetes 2014, 63:832-834.
53. Sachdeva M.M., Stoffers D.A. Minireview: meeting the demand for insulin: molecular mechanisms of adaptive postnatal ß-cell mass expansion. Mol Endocrinol 2009, 23:747-758.
54. Linnemann A.K., Baan M., Davis D.B. Pancreatic β-cell proliferation in obesity. Adv Nutr 2014, 5:278-288.
55. Gargani S., Thévenet J., Yuan J.E., et al. Adaptive changes of human islets to an obesogenic environment in the mouse. Diabetologia 2013, 56:350-358.
56. Brelje T.C., Bhagroo N.V., Stout L.E., Sorenson R.L. Beneficial effects of lipids and prolactin on insulin secretion and beta-cell proliferation: a role for lipids in the adaptation of islets to pregnancy. J Endocrinol 2008, 197:265-276.
57. Oh Y.S. Mechanistic insights into pancreatic beta-cell mass regulation by glucose and free fatty acids. Anat Cell Biol 2015, 48:16-24.
58. Milburn J.L., Hirose H., Lee Y.H., et al. Pancreatic beta-cells in obesity. Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids. J Biol Chem 1995, 270(3):1295-1299.
59. Steil G.M., Trivedi N., Jonas J.-C., et al. Adaptation of beta-cell mass to substrate oversupply: enhanced function with normal gene expression. Am J Physiol Endocrinol Metab 2001, 280:E788-E796.
60. Fontés G., Zarrouki B., Hagman D.K., et al. Glucolipotoxicity age-dependently impairs beta cell function in rats despite a marked increase in beta cell mass. Diabetologia 2010, 53(11):2369-2379.
61. Van Citters G.W., Kabir M., Kim S.P., et al. Elevated glucagon-like peptide-1-(7-36)-amide, but not glucose, associated with hyperinsulinemic compensation for fat feeding. J Clin Endocrinol Metab 2002, 87:5191-5198.
62. Drucker D.J. The biology of incretin hormones. Cell Metab 2006, 3(3):153-165.
63. Moffett R.C., Vasu S., Flatt P.R. Functional GIP receptors play a major role in islet compensatory response to high fat feeding in mice. Biochim Biophys Acta 2015, 1850:1206-1214.
64. McIntosh C.H., Widenmaier S., Kim S.J. Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide; GIP). Vitam Horm 2009, 80:409-471.
65. Buteau J. GLP-1 receptor signaling: effects on pancreatic beta-cell proliferation and survival. Diabetes Metab 2008, 34(Suppl. 2):S73-S77.
66. Song W.-J., Schreiber W.E., Zhong E., et al. Exendin-4 stimulation of cyclin A2 in β-cell proliferation. Diabetes 2008, 57:2371-2381.
67. Persaud S.J., Liu B., Sampaio H.B., Jones P.M., Muller D.S. Calcium/calmodulin-dependent kinase IV controls glucose-induced Irs2 expression in mouse beta cells via activation of cAMP response element-binding protein. Diabetologia 2011, 54(5):1109-1120.
68. Ahrén B., Carr R.D., Deacon C.F. Incretin hormone secretion over the day. Vitam Horm 2010, 84:203-220.
69. Topp B.G., McArthur M.D., Finegood D.T. Metabolic adaptations to chronic glucose infusion in rats. Diabetologia 2004, 47(9):1602-1610.
70. Alonso L.C., Yokoe T., Zhang P., et al. Glucose infusion in mice a new model to induce β-cell replication. Diabetes 2007, 56:1792-1801.
71. Levitt H.E., Cyphert T.J., Pascoe J.L., et al. Glucose stimulates human beta cell replication in vivo in islets transplanted into NOD-severe combined immunodeficiency (SCID) mice. Diabetologia 2011, 54(3):572-582.
72. Liu H., Remedi M.S., Pappan K.L., et al. Glycogen synthase kinase-3 and mammalian target of rapamycin pathways contribute to DNA synthesis, cell cycle progression, and proliferation in human islets. Diabetes 2009, 58:663-672.
73. Rohatgi N., Aly H., Marshall C.A., et al. Novel insulin sensitizer modulates nutrient sensing pathways and maintains b- cell phenotype in human islets. PLoS One 2013, 8:e62012.
74. Terauchi Y., Takamoto I., Kubota N., et al. Glucokinase and IRS-2 are required for compensatory β-cell hyperplasia in response to high-fat diet-induced insulin resistance. J Clin Invest 2007, 117(1):246-257.
75. Nakamura A., Terauchi Y., Ohyama S., et al. Impact of small-molecule glucokinase activator on glucose metabolism and β-cell mass. Endocrinology 2009, 150:1147-1154.
76. Wei P., Shi M., Barnum S., Cho H., Carlson T., Fraser J.D. Effects of glucokinase activators GKA50 and LY2121260 on proliferation and apoptosis in pancreatic INS-1 beta cells. Diabetologia 2009, 52:2142-2150.
77. Oh Y.S., Lee Y.-J., Park K., Choi H.H., Yoo S., Jun H.-S. Treatment with glucokinase activator, YH-GKA, increases cell proliferation and decreases glucotoxic apoptosis in INS-1 cells. Eur J Pharm Sci 2014, 51:137-145.
78. Bernal-Mizrachi E., Kulkarni R.N., Scott D.K., et al. Human beta-cell proliferation and intracellular signaling part 2: still driving in the dark without a road map. Diabetes 2014, 63(3):819-831.
79. Liu Y., Tanabe K., Baronnier D., et al. Conditional ablation of Gsk-3b in islet beta cells results in expanded mass and resistance to fat feeding-induced diabetes in mice. Diabetologia 2010, 53:2600-2610.
80. Vidal-Puig A., Jimenez-Liñan M., Lowell B.B., et al. Regulation of PPAR gamma gene expression by nutrition and obesity in rodents. J Clin Invest 1996, 97:2553-2561.
81. Rosen E.D., Kulkarni R.N., Sarraf P., et al. Targeted elimination of peroxisome proliferator activated receptor in beta cells leads to abnormalities in islet mass without compromising glucose homeostasis. Mol Cell Biol 2003, 23:7222-7229.
82. Medina-Gomez G., Gray S.L., Yetukuri L., et al. PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet 2007, 3(4):e64.
83. Shafrir E., Ziv E., Mosthaf L. Nutritionally induced insulin resistance and receptor defect leading to beta-cell failure in animal models. Ann N Y Acad Sci 1999, 892:223-246.
84. Falcão V.T., Oliveira R.B., Maschio D.A., Carvalho C.P., Collares-Buzato C.B. Cellular distribution and expression of cell adhesion molecules (CAMs) in pancreatic islet cells of obese and diabetic mice. Mol Biol Cell 2014, 25:448. (abstract #P591).
85. Montane J., Cadavez L., Novials A. Stress and the inflammatory process: a major cause of pancreatic cell death in type 2 diabetes. Diabetes Metab Syndr Obes 2014, 7:25-34.
86. Kaneto H., Matsuoka T. Role of pancreatic transcription factors in maintenance of mature β-cell function. Int J Mol Sci 2015, 16:6281-6297.
87. Sauter N.S., Thienel C., Plutino Y., et al. Angiotensin II induces interleukin-1β-mediated islet inflammation and beta-cell dysfunction independently of vasoconstrictive effects. Diabetes 2015, 64:1273-1283.
88. Tangvarasittichai S. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes 2015, 6(3):456-480.
89. Butler A.E., Janson J., Bonner-Weir S., Ritzel R., Rizza R.A., Butler P.C. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003, 52:102-110.
90. Yoon K.H., Ko S.H., Cho J.H., et al. Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 2003, 88:2300-2308.
91. Deng S., Vatamaniuk M., Huang X., et al. Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects. Diabetes 2004, 53:624-632.
92. Gunton J.E., Kulkarni R.N., Yim S., et al. Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell 2005, 122:337-349.
93. Carpentier A., Mittelman S.D., Bergman R.N., Giacca A., Lewis G.F. Prolonged elevation of plasma free fatty acids impairs pancreatic β-cell function in obese nondiabetic humans but not in individuals with type 2 diabetes. Cell 2000, 49:399-408.
94. Poitout V. Glucolipotoxicity of the pancreatic beta-cell: myth or reality?. Biochem Soc Trans 2008, 36(Pt 5):901-904.
95. Poitout V., Robertson R.P. Glucolipotoxicity: fuel excess and β-cell dysfunction. Endocr Rev 2008, 29(3):351-366.
96. Del Prato S. Role of glucotoxicity and lipotoxicity in the pathophysiology of type 2 diabetes mellitus and emerging treatment strategies. Diabet Med 2009, 26:1185-1192.
97. Asghar Z., Yau D., Chan F., Leroith D., Chan C.B., Wheeler M.B. Insulin resistance causes increased beta-cell mass but defective glucose-stimulated insulin secretion in a murine model of type 2 diabetes. Diabetologia 2006, 49:90-99.
98. Schofield C.J., Sutherland C. Disordered insulin secretion in the development of insulin resistance and type 2 diabetes. Diabet Med 2012, 29(8):972-979.
99. Del Guerra S., Lupi R., Marselli L., et al. Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes 2005, 54(3):727-735.
100. Serre-Beinier V., Bosco D., Zulianello L., et al. Cx36 makes channels coupling human pancreatic beta-cells, and correlates with insulin expression. Hum Mol Genet 2009, 18:428-439.
101. 2+ oscillations and insulin secretion in MIN6 cells. Diabetes 2003, 52:417-424.
102. 2+ and insulin oscillations, and basal insulin release. Diabetes 2005, 54:1798-1807.
103. Allagnat F., Martin D., Condorelli D.F., Waeber G., Haefliger J.A. Glucose represses connexin36 in insulin-secreting cells. J Cell Sci 2005, 118:5335-5344.
104. Allagnat F., Alonso F., Martin D., Abderrahmani A., Waeber G., Haefliger J.A. ICER-1gamma overexpression drives palmitate-mediated connexin36 down-regulation in insulin-secreting cells. J Biol Chem 2008, 283:5226-5234.
105. Ma Z., Wirström T., Borg L.A., et al. Diabetes reduces β-cell mitochondria and induces distinct morphological abnormalities, which are reproducible by high glucose in vitro with attendant dysfunction. Islets 2012, 4(3):233-242.
106. Lu H., Koshkin V., Allister E.M., Gyulkhandanyan A.V., Wheeler M.B. Molecular and metabolic evidence for mitochondrial defects associated with β-cell dysfunction in a mouse model of type 2 diabetes. Diabetes 2010, 59:448-459.
107. Kaneto H., Xu G., Fujii N., Kim S., Bonner-Weir S., Weir G.C. Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem 2002, 277(33):30010-30018.
108. Matsuoka T., Kaneto H., Miyatsuka T., et al. Regulation of MafA expression in pancreatic β-cells in db/db mice with diabetes. Diabetes 2010, 59:1709-1720.
109. Matsuoka T., Kaneto H., Kawashima S., et al. Preserving MafA expression in diabetic islet β-cells improves glycemic control in vivo. J Biol Chem 2015, 290(12):7647-7657.
110. Shu L., Matveyenko A.V., Kerr-Conte J., Cho J.H., McIntosh C.H., Maedler K. Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function. Hum Mol Genet 2009, 18:2388-2399.
111. Xu G., Kaneto H., Laybutt D.R., et al. Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to the impaired incretin effects in diabetes. Diabetes 2007, 56:1551-1558.
112. Kang Z.F., Deng Y., Zhou Y., et al. Pharmacological reduction of NEFA restores the efficacy of incretin-based therapies through GLP-1 receptor signalling in the beta cell in mouse models of diabetes. Diabetologia 2013, 56:423-433.
113. Sun J., Cui J., He Q., Chen Z., Arvan P., Liu M. Proinsulin misfolding and endoplasmic reticulum stress during the development and progression of diabetes. Mol Asp Med 2015, 42:105-118.
114. Giacca A., Xiao C., Oprescu A.I., Carpentier A.C., Lewis G.F. Lipid-induced pancreatic β-cell dysfunction: focus on in vivo studies. Am J Physiol Endocrinol Metab 2011, 300:E255-E262.
115. Marchetti P., Bugliani M., Lupi R., et al. The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients. Diabetologia 2007, 50:2486-2494.
116. Tiedge M., Lortz S., Drinkgern J., Lenzen S. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 1997, 46(11):1733-1742.
117. Boschero A.C., Stoppiglia L.F., Collares-Buzato C.B., Bosqueiro J.R., Delghingaro-Augusto V., Leite A., et al. Expression of a thioredoxin peroxidase in insulin-producing cells. Diabetes Metab 2002, 28(6 Pt 2). 3S25-3S28.
118. Ihara Y., Toyokuni S., Uchida K., et al. Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. Diabetes 1999, 48(4):927-932.
119. Tanaka Y., Tran P.O., Harmon J., Robertson R.P. A role for glutathione peroxidase in protecting pancreatic beta cells against oxidative stress in a model of glucose toxicity. Proc Natl Acad Sci USA 2002, 99(19):12363-12368.
120. Koulajian K., Ivovic A., Ye K., et al. Overexpression of glutathione peroxidase 4 prevents β-cell dysfunction induced by prolonged elevation of lipids in vivo. Am J Physiol Endocrinol Metab 2013, 305:E254-E262.
121. Donath M.Y., Dalmas E., Sauter N.S., Boni-Schnetzler M. Inflammation in obesity and diabetes: islet dysfunction and therapeutic opportunity. Cell Metab 2013, 17(6):860-872.
122. Ehses J.A., Perren A., Eppler E., et al. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 2007, 56:2356-2370.
123. Marselli L., Dotta F., Piro S., et al. Th2 cytokines have a partial, direct protective effect on the function and survival of isolated human islets exposed to combined proinflammatory and Th1 cytokines. J Clin Endocrinol Metab 2001, 86(10):4974-4978.
124. Zaitseva I.I., Hultcrantz M., Sharoyko V., Flodstrom-Tullberg M., Zaitsev S.V., Berggren P.O. Suppressor of cytokine signaling-1 inhibits caspase activation and protects from cytokine-induced beta cell death. Cell Mol Life Sci 2009, 66(23):3787-3795.
125. Ehses J.A., Meier D.T., Wueest S., et al. Toll-like receptor 2-deficient mice are protected from insulin resistance and beta cell dysfunction induced by a high-fat diet. Diabetologia 2010, 53:1795-1806.
126. Larsen C.M., Faulenbach M., Vaag A., et al. Interleukin-1-Receptor antagonist in type 2 diabetes mellitus. N Engl J Med 2007, 356:1517-1526.
127. van Asseldonk E.J., Stienstra R., Koenen T.B., Joosten L.A., Netea M.G., Tack C.J. Treatment with Anakinra improves disposition index but not insulin sensitivity in nondiabetic subjects with the metabolic syndrome: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2011, 96(7):2119-2126.
128. Mahdi T., Hanzelmann S., Salehi A., et al. Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes. Cell Metab 2012, 16:625-633.
129. Ferdaoussi M., Abdelli S., Yang J.-Y., et al. Exendin-4 protects β-cells from interleukin-1 beta-induced apoptosis by interfering with the c-Jun NH2-terminal kinase pathway. Diabetes 2008, 57(5):1205-1215.
130. Chin-Chance C.V.T., Newman M.V., Aronovitz A., et al. Role of the mitogen-activated protein kinases in cytokine-mediated inhibition of insulin gene expression. J Invest Med 2006, 54(3):132-142.
131. Abdelli S., Abderrahmani A., Hering B.J., Beckmann J.S., Bonny C. The c-Jun N-terminal kinase JNK participates in cytokine- and isolation stress-induced rat pancreatic islet apoptosis. Diabetologia 2007, 50(8):1660-1669.
132. Grunnet L.G., Aikin R., Tonnesen M.F., et al. Proinflammatory cytokines activate the intrinsic apoptotic pathway in β-cells. Diabetes 2009, 58:1807-1815.
133. Verma G., Datta M. The critical role of JNK in the ER-mitochondrial crosstalk during apoptotic cell death. J Cell Physiol 2012, 227:1791-1795.