First phase insulin secretion and type 2 diabetes

Current Molecular Medicine

Volumn 13, Issue 1, 2013, Pages 126-139

  Cheng, K ^a,b   Andrikopoulos, S ^c   Gunton, J E ^a,d,e  

^a GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

^b UNIVERSITY OF NEW SOUTH WALES   (Australia)

^c UNIVERSITY OF MELBOURNE   (Australia)

^d UNIVERSITY OF SYDNEY   (Australia)

^e WESTMEAD HOSPITAL   (Australia)

Author keywords

Aryl hydrocarbon nuclear translocator; Glucose homeostasis; Hypoxia inducible factor 1 ; Insulin secretion; Regulatory genes; Type 2 diabetes

Indexed keywords

ADENOSINE TRIPHOSPHATE SENSITIVE POTASSIUM CHANNEL; C PEPTIDE; FRUCTOSE BISPHOSPHATASE; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; GLUCOKINASE; GLUCOSE TRANSPORTER 2; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INSULIN RECEPTOR; MITOCHONDRIAL TRANSCRIPTION FACTOR A; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; ROTENONE; SIRTUIN; TRANSCRIPTION FACTOR PDX 1; UNCOUPLING PROTEIN 1; UNCOUPLING PROTEIN 2; UNCOUPLING PROTEIN 3; VOLTAGE GATED CALCIUM CHANNEL; VON HIPPEL LINDAU PROTEIN; GLUCOSE; HIF1A PROTEIN, HUMAN; INSULIN; NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) TRANSHYDROGENASE; VHL PROTEIN, HUMAN;

CITRIC ACID CYCLE; GENETIC ASSOCIATION; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLYCOLYSIS; HUMAN; INSULIN RELEASE; INTRAVENOUS GLUCOSE TOLERANCE TEST; NON INSULIN DEPENDENT DIABETES MELLITUS; OXIDATIVE PHOSPHORYLATION; REGULATOR GENE; REVIEW; GENETICS; METABOLISM; SECRETION (PROCESS);

DIABETES MELLITUS, TYPE 2; GENOME-WIDE ASSOCIATION STUDY; GLUCOKINASE; GLUCOSE; GLYCOLYSIS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; INSULIN; NADP TRANSHYDROGENASES; OXIDATIVE PHOSPHORYLATION; RECEPTOR, INSULIN; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 84881372194     PISSN: 15665240     EISSN: 18755666     Source Type: Journal    
DOI: 10.2174/156652413804486287     Document Type: Review

References (160)

1. Kaiyala KJ, Prigeon RL, Kahn SE, Woods SC, Porte D, Jr., Schwartz MW. Reduced beta-cell function contributes to impaired glucose tolerance in dogs made obese by high-fat feeding. Am J Physiol 1999; 277(4 Pt 1): E659-67.
2. Kasuga M. Insulin resistance and pancreatic beta cell failure. J Clin Invest 2006; 116(7): 1756-60.
3. Voight BF, Scott LJ, Steinthorsdottir V, et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 2010; 42(7): 579-89.
4. Zeggini E, Scott LJ, Saxena R, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 2008; 40(5): 638-45.
5. Bunt JC, Krakoff J, Ortega E, Knowler WC, Bogardus C. Acute insulin response is an independent predictor of type 2 diabetes mellitus in individuals with both normal fasting and 2-h plasma glucose concentrations. Diabetes Metab Res Rev 2007; 23(4): 304-10.
6. Vranic M, Fono P, Kovacevic N, Lin BJ. Glucose kinetics and fatty acids in dogs on matched insulin infusion after glucose load. Metabolism 1971; 20(10): 954-67.
7. Del Prato S, Tiengo A. The importance of first-phase insulin secretion: implications for the therapy of type 2 diabetes mellitus. Diabetes Metab Res Rev 2001; 17(3): 164-74.
8. Pratley RE, Weyer C. The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus. Diabetologia 2001; 44(8): 929-45.
9. Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 1999; 104(6): 787-94.
10. Lalic NM, Maric J, Svetel M, et al. Glucose homeostasis in Huntington disease: abnormalities in insulin sensitivity and early-phase insulin secretion. Arch Neurol 2008; 65(4): 476-80.
11. Ronnemaa E, Zethelius B, Sundelof J, et al. Impaired insulin secretion increases the risk of Alzheimer disease. Neurology 2008; 71(14): 1065-71.
12. Kahn CB, Soeldner JS, Gleason RE, Rojas L, Camerini-Davalos RA, Marble A. Clinical and chemical diabetes in offspring of diabetic couples. N Engl J Med 1969; 281(7): 343-7.
13. Gerich JE. Metabolic abnormalities in impaired glucose tolerance. Metabolism 1997; 46(12 Suppl 1): 40-3.
14. Pimenta W, Mitrakou A, Jensen T, Yki-Jarvinen H, Daily G, Gerich J. Insulin secretion and insulin sensitivity in people with impaired glucose tolerance. Diabet Med 1996; 13(9 Suppl 6): S33-6.
15. Yoneda H, Ikegami H, Yamamoto Y, et al. Analysis of earlyphase insulin responses in nonobese subjects with mild glucose intolerance. Diabetes Care 1992; 15(11): 1517-21.
16. Curry DL, Bennett LL, Grodsky GM. Dynamics of insulin secretion by the perfused rat pancreas. Endocrinology 1968; 83(3): 572-84.
17. Calles-Escandon J, Robbins DC. Loss of early phase of insulin release in humans impairs glucose tolerance and blunts thermic effect of glucose. Diabetes 1987; 36(10): 1167-72.
18. Matthews DR, Naylor BA, Jones RG, Ward GM, Turner RC. Pulsatile insulin has greater hypoglycemic effect than continuous delivery. Diabetes 1983; 32(7): 617-21.
19. Hansen BC, Jen KC, Belbez Pek S, Wolfe RA. Rapid oscillations in plasma insulin, glucagon, and glucose in obese and normal weight humans. J Clin Endocrinol Metab 1982; 54(4): 785-92.
20. Cunningham BA, Deeney JT, Bliss CR, Corkey BE, Tornheim K. Glucose-induced oscillatory insulin secretion in perifused rat pancreatic islets and clonal beta-cells (HIT). Am J Physiol 1996; 271(4 Pt 1): E702-10.
21. Hellman B, Gylfe E, Bergsten P, Grapengiesser E, Lund PE, Berts A, et al. The role of Ca2+ in the release of pancreatic islet hormones. Diabete Metab 1994; 20(2): 123-31.
22. Jung SK, Kauri LM, Qian WJ, Kennedy RT. Correlated oscillations in glucose consumption, oxygen consumption, and intracellular free Ca(2+) in single islets of Langerhans. J Biol Chem 2000; 275(9): 6642-50.
23. Polonsky KS, Given BD, Hirsch LJ, et al. Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. N Engl J Med 1988; 318(19): 1231-9.
24. 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): 727-35.
25. O'Rahilly S, Turner RC, Matthews DR. Impaired pulsatile secretion of insulin in relatives of patients with non-insulin- dependent diabetes. N Engl J Med 1988; 318(19): 1225-30.
26. Aoki TT, Grecu EO, Arcangeli MA, Benbarka MM, Prescott P, Ahn JH. Chronic intermittent intravenous insulin therapy: a new frontier in diabetes therapy. Diabetes Technol Ther 2001; 3(1): 111-23.
27. Mirbolooki MR, Taylor GE, Knutzen VK, Scharp DW, Willcourt R, Lakey JR. Pulsatile intravenous insulin therapy: the best practice to reverse diabetes complications? Med Hypotheses 2009; 73(3): 363-9.
28. Bergman RN, Phillips LS, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest 1981; 68(6): 1456-67.
29. Elahi D. In praise of the hyperglycemic clamp. A method forassessment of beta-cell sensitivity and insulin resistance. Diabetes Care 1996; 19(3): 278-86.
30. Bacha F, Gungor N, Arslanian SA. Measures of beta-cell function during the oral glucose tolerance test, liquid mixed- meal test, and hyperglycemic clamp test. J Pediatr 2008; 152(5): 618-21.
31. Greenbaum CJ, Mandrup-Poulsen T, McGee PF, et al. Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes. Diabetes Care 2008; 31(10): 1966-71.
32. Caumo A, Luzi L. First-phase insulin secretion: does it exist in real life? Considerations on shape and function. Am J Physiol Endocrinol Metab 2004; 287(3): E371-85.
33. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237(3): E214-23.
34. Henquin JC. Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 2000; 49(11): 1751-60.
35. Henquin JC, Ravier MA, Nenquin M, Jonas JC, Gilon P. Hierarchy of the beta-cell signals controlling insulin secretion. Eur J Clin Invest 2003; 33(9): 742-50.
36. Straub SG, Sharp GW. Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes Metab Res Rev 2002; 18(6): 451-63.
37. Newgard CB, McGarry JD. Metabolic coupling factors in pancreatic beta-cell signal transduction. Annu Rev Biochem 1995; 64: 689-719.
38. Ashcroft FM, Harrison DE, Ashcroft SJ. Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells. Nature 1984; 312(5993): 446-8.
39. Cook DL, Hales CN. Intracellular ATP directly blocks K+channels in pancreatic B-cells. Nature 1984; 311(5983): 271-3.
40. Kelly RP, Sutton R, Ashcroft FM. Voltage-activated calcium and potassium currents in human pancreatic beta-cells. J Physiol 1991; 443: 175-92.
41. Gembal M, Gilon P, Henquin JC. Evidence that glucose can control insulin release independently from its action on ATP- sensitive K+ channels in mouse B cells. J Clin Invest 1992; 89(4): 1288-95.
42. Sato Y, Aizawa T, Komatsu M, Okada N, Yamada T. Dual functional role of membrane depolarization/Ca2+ influx in rat pancreatic B-cell. Diabetes 1992; 41(4): 438-43.
43. Nolan CJ, Madiraju MS, Delghingaro-Augusto V, Peyot ML, Prentki M. Fatty acid signaling in the beta-cell and insulin secretion. Diabetes 2006; 55 Suppl 2: S16-23.
44. Henquin JC, Nenquin M, Stiernet P, Ahren B. In vivo and in vitro glucose-induced biphasic insulin secretion in the mouse: pattern and role of cytoplasmic Ca2+ and amplification signals in beta-cells. Diabetes 2006; 55(2): 441-51.
45. Proks P, Eliasson L, Ammala C, Rorsman P, Ashcroft FM. Ca(2+)- and GTP-dependent exocytosis in mouse pancreatic beta-cells involves both common and distinct steps. J Physiol 1996; 496 (Pt 1): 255-64.
46. Barg S, Eliasson L, Renstrom E, Rorsman P. A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse beta-cells. Diabetes 2002; 51 Suppl 1: S74-82.
47. Parsons TD, Coorssen JR, Horstmann H, Almers W. Docked granules, the exocytic burst, and the need for ATP hydrolysis in endocrine cells. Neuron 1995; 15(5): 1085-96.
48. Eliasson L, Renstrom E, Ding WG, Proks P, Rorsman P. Rapid ATP-dependent priming of secretory granules precedes Ca(2+)-induced exocytosis in mouse pancreatic B- cells. J Physiol 1997; 503 (Pt 2): 399-412.
49. Stryer L. Biochemistry. 4th ed. New York: W. H. Freeman and Company; 1995.
50. Liang Y, Bai G, Doliba N, et al. Glucose metabolism and insulin release in mouse beta HC9 cells, as model for wild- type pancreatic beta-cells. Am J Physiol 1996; 270(5 Pt 1): E846-57.
51. Maechler P, Kennedy ED, Pozzan T, Wollheim CB. Mitochondrial activation directly triggers the exocytosis of insulin in permeabilized pancreatic beta-cells. Embo J 1997; 16(13): 3833-41.
52. Sekine N, Cirulli V, Regazzi R, et al. Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic beta-cells. Potential role in nutrient sensing. J Biol Chem 1994; 269(7): 4895-902.
53. Gauthier BR, Wiederkehr A, Baquie M, et al. PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression. Cell Metab 2009; 10(2): 110-8.
54. Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science 2005; 307(5708): 384-7.
55. Silva JP, Kohler M, Graff C, et al. Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes. Nat Genet 2000; 26(3): 336-40.
56. Scarpulla RC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 2008; 88(2): 611-38.
57. Matschinsky FM, Ellerman J. Dissociation of the insulin releasing and the metabolic functions of hexoses in islets of Langerhans. Biochem Biophys Res Commun 1973; 50(2): 193-9.
58. Gray JP, Heart E. Usurping the mitochondrial supremacy: extramitochondrial sources of reactive oxygen intermediates and their role in beta cell metabolism and insulin secretion. Toxicol Mech Methods 2010; 20(4): 167-74.
59. Mertz RJ, Worley JF, Spencer B, Johnson JH, Dukes ID. Activation of stimulus-secretion coupling in pancreatic beta- cells by specific products of glucose metabolism. Evidence for privileged signaling by glycolysis. J Biol Chem 1996; 271(9): 4838-45.
60. Sener A, Kawazu S, Hutton JC, et al. The stimulus-secretion coupling of glucose-induced insulin release. Effect of exogenous pyruvate on islet function. Biochem J 1978; 176(1): 217-32.
61. Sener A, Malaisse WJ. Stimulation by D-glucose of mitochondrial oxidative events in islet cells. Biochem J 1987; 246(1): 89-95.
62. Lambert AJ, Brand MD. Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane. Biochem J 2004; 382(Pt 2): 511-7.
63. Quinn MT, Gauss KA. Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases. J Leukoc Biol 2004; 76(4): 760-81.
64. Crane FL, Low H. Reactive oxygen species generation at the plasma membrane for antibody control. Autoimmun Rev 2008; 7(7): 518-22.
65. Pi J, Bai Y, Zhang Q, et al. Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes 2007; 56(7): 1783-91.
66. Sakai K, Matsumoto K, Nishikawa T, et al. Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells. Biochem Biophys Res Commun 2003; 300(1): 216-22.
67. Ebelt H, Peschke D, Bromme HJ, Morke W, Blume R, Peschke E. Influence of melatonin on free radical-induced changes in rat pancreatic beta-cells in vitro. J Pineal Res 2000; 28(2): 65-72.
68. Leloup C, Tourrel-Cuzin C, Magnan C, et al. Mitochondrial reactive oxygen species are obligatory signals for glucose- induced insulin secretion. Diabetes 2009; 58(3): 673-81.
69. Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ. Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem 2003; 278(38): 36027-31.
70. Pierce M, Keen H, Bradley C. Risk of diabetes in offspring of parents with non-insulin-dependent diabetes. Diabet Med 1995; 12(1): 6-13.
71. Newman B, Selby JV, King MC, Slemenda C, Fabsitz R, Friedman GD. Concordance for type 2 (non-insulin- dependent) diabetes mellitus in male twins. Diabetologia 1987; 30(10): 763-8.
72. Scott LJ, Mohlke KL, Bonnycastle LL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 2007; 316(5829): 1341-5.
73. Sladek R, Rocheleau G, Rung J, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 2007; 445(7130): 881-5.
74. da Silva Xavier G, Loder MK, McDonald A, et al. TCF7L2 regulates late events in insulin secretion from pancreatic islet beta-cells. Diabetes 2009; 58(4): 894-905.
75. Lemaire K, Ravier MA, Schraenen A, et al. Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice. Proc Natl Acad Sci USA 2009; 106(35): 14872-7.
76. Nicolson TJ, Bellomo EA, Wijesekara N, et al. Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes- associated variants. Diabetes 2009; 58(9): 2070-83.
77. Zatyka M, Ricketts C, da Silva Xavier G, et al. Sodium-potassium ATPase 1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress. Hum Mol Genet 2008; 17(2): 190-200.
78. Palmer ND, Lehtinen AB, Langefeld CD, et al. Association of TCF7L2 gene polymorphisms with reduced acute insulin response in Hispanic Americans. J Clin Endocrinol Metab 2008; 93(1): 304-9.
79. Gould GW, Holman GD. The glucose transporter family: structure, function and tissue-specific expression. Biochem J 1993; 295 (Pt 2): 329-41.
80. Efrat S, Tal M, Lodish HF. The pancreatic beta-cell glucose sensor. Trends Biochem Sci 1994; 19(12): 535-8.
81. Thorens B, Weir GC, Leahy JL, Lodish HF, Bonner-Weir S. Reduced expression of the liver/beta-cell glucose transporter isoform in glucose-insensitive pancreatic beta cells of diabetic rats. Proc Natl Acad Sci USA 1990; 87(17): 6492-6.
82. Johnson JH, Ogawa A, Chen L, et al. Underexpression of beta cell high Km glucose transporters in noninsulin- dependent diabetes. Science 1990; 250(4980): 546-9.
83. Thorens B, Wu YJ, Leahy JL, Weir GC. The loss of GLUT2 expression by glucose-unresponsive beta cells of db/db mice is reversible and is induced by the diabetic environment. J Clin Invest 1992; 90(1): 77-85.
84. Guillam MT, Hummler E, Schaerer E, et al. Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nat Genet 1997; 17(3): 327-30.
85. Santer R, Schneppenheim R, Dombrowski A, Gotze H, Steinmann B, Schaub J. Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi- Bickel syndrome. Nat Genet 1997; 17(3): 324-6.
86. Mueckler M, Kruse M, Strube M, Riggs AC, Chiu KC, Permutt MA. A mutation in the Glut2 glucose transporter gene of a diabetic patient abolishes transport activity. J Biol Chem 1994; 269(27): 17765-7.
87. Unger RH. Diabetic hyperglycemia: link to impaired glucose transport in pancreatic beta cells. Science 1991; 251(4998): 1200-5.
88. Ferrer J, Benito C, Gomis R. Pancreatic islet GLUT2 glucose transporter mRNA and protein expression in humans with and without NIDDM. Diabetes 1995; 44(12): 1369-74.
89. Gunton JE, Kulkarni RN, Yim S, et al. Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell 2005; 122(3): 337-49.
90. McCulloch LJ, van de Bunt M, Braun M, Frayn KN, Clark A, Gloyn AL. 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.
91. Grupe A, Hultgren B, Ryan A, Ma YH, Bauer M, Stewart TA. Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis. Cell 1995; 83(1): 69-78.
92. Froguel P, Vaxillaire M, Sun F, Velho G, Zouali H, Butel MO, et al. Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. Nature 1992; 356(6365): 162-4.
93. Velho G, Blanche H, Vaxillaire M, et al. Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families. Diabetologia 1997; 40(2): 217-24.
94. Hattersley AT, Turner RC, Permutt MA, et al. Linkage of type 2 diabetes to the glucokinase gene. Lancet 1992; 339(8805): 1307-10.
95. Aizawa T, Asanuma N, Terauchi Y, et al. Analysis of the pancreatic beta cell in the mouse with targeted disruption of the pancreatic beta cell-specific glucokinase gene. Biochem Biophys Res Commun 1996; 229(2): 460-5.
96. Bali D, Svetlanov A, Lee HW, et al. Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene. J Biol Chem 1995; 270(37): 21464-7.
97. Ishihara H, Tashiro F, Ikuta K, et al. Inhibition of pancreatic beta-cell glucokinase by antisense RNA expression in transgenic mice: mouse strain-dependent alteration of glucose tolerance. FEBS Lett 1995; 371(3): 329-32.
98. Sakura H, Ashcroft SJ, Terauchi Y, Kadowaki T, Ashcroft FM. Glucose modulation of ATP-sensitive K-currents in wild- type, homozygous and heterozygous glucokinase knock-out mice. Diabetologia 1998; 41(6): 654-9.
99. Gorman T, Hope DC, Brownlie R, et al. Effect of high-fat diet on glucose homeostasis and gene expression in glucokinase knockout mice. Diabetes Obes Metab 2008; 10(10): 885-97.
100. Aguilar-Bryan L, Bryan J. Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev 1999; 20(2): 101-35.
101. Seghers V, Nakazaki M, DeMayo F, Aguilar-Bryan L, Bryan J. Sur1 knockout mice. A model for K(ATP) channel- independent regulation of insulin secretion. J Biol Chem 2000; 275(13): 9270-7.
102. Miki T, Nagashima K, Tashiro F, et al. Defective insulin secretion and enhanced insulin action in KATP channel- deficient mice. Proc Natl Acad Sci USA 1998; 95(18): 10402-6.
103. Thomas PM, Cote GJ, Wohllk N, et al. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science 1995; 268(5209): 426-9.
104. Dunne MJ, Kane C, Shepherd RM, et al. Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor. N Engl J Med 1997; 336(10): 703-6.
105. Nestorowicz A, Inagaki N, Gonoi T, et al. A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism. Diabetes 1997; 46(11): 1743-8.
106. Norman M, Moldovan S, Seghers V, Wang XP, DeMayo FJ, Brunicardi FC. Sulfonylurea receptor knockout causes glucose intolerance in mice that is not alleviated by concomitant somatostatin subtype receptor 5 knockout. Ann Surg 2002; 235(6): 767-74.
107. Ravier MA, Nenquin M, Miki T, Seino S, Henquin JC. Glucose controls cytosolic Ca2+ and insulin secretion in mouse islets lacking adenosine triphosphate-sensitive K+ channels owing to a knockout of the pore-forming subunit Kir6.2. Endocrinology 2009; 150(1): 33-45.
108. Andrikopoulos S, Rosella G, Gaskin E, et al. Impaired regulation of hepatic fructose-1,6-bisphosphatase in the New Zealand obese mouse model of NIDDM. Diabetes 1993; 42(12): 1731-6.
109. Lan H, Rabaglia ME, Stoehr JP, et al. Gene expression profiles of nondiabetic and diabetic obese mice suggest a role of hepatic lipogenic capacity in diabetes susceptibility. Diabetes 2003; 52(3): 688-700.
110. Andrikopoulos S, Proietto J. The biochemical basis of increased hepatic glucose production in a mouse model of type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1995; 38(12): 1389-96.
111. Kebede M, Favaloro J, Gunton JE, et al. Fructose-1,6-bisphosphatase overexpression in pancreatic beta-cells results in reduced insulin secretion: a new mechanism for fat- induced impairment of beta-cell function. Diabetes 2008; 57(7): 1887-95.
112. Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 1992; 12(12): 5447-54.
113. Noordeen NA, Khera TK, Sun G, et al. Carbohydrate-responsive element-binding protein (ChREBP) is a negative regulator of ARNT/HIF-1beta gene expression in pancreatic islet beta-cells. Diabetes 2010; 59(1): 153-60.
114. Schofield CJ, Ratcliffe PJ. Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 2004; 5(5): 343-54.
115. Cheng K, Ho K, Stokes R, et al. Hypoxia-inducible factor1alpha regulates beta cell function in mouse and human islets. J Clin Invest 2010; 120(6): 2171-83.
116. Ivan M, Kondo K, Yang H, et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 2001; 292(5516): 464-8.
117. Cantley J, Selman C, Shukla D, et al. Deletion of the von Hippel-Lindau gene in pancreatic beta cells impairs glucose homeostasis in mice. J Clin Invest 2009; 119(1): 125-35.
118. Choi D, Cai EP, Schroer SA, Wang L, Woo M. Vhl is required for normal pancreatic beta cell function and the maintenance of beta cell mass with age in mice. Lab Invest 2011; 91(4): 527-38.
119. Puri S, Cano DA, Hebrok M. A role for von Hippel-Lindau protein in pancreatic beta-cell function. Diabetes 2009; 58(2): 433-41.
120. Zehetner J, Danzer C, Collins S, et al. pVHL is a regulator of glucose metabolism and insulin secretion in pancreatic {beta} cells. Genes Dev 2008; 22(22): 3135-46.
121. Chandel NS, McClintock DS, Feliciano CE, et al. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem 2000; 275(33): 25130-8.
122. Guzy RD, Hoyos B, Robin E, et al. Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab 2005; 1(6): 401-8.
123. Goyal P, Weissmann N, Grimminger F, et al. Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species. Free Radic Biol Med 2004; 36(10): 1279-88.
124. Zhang N, Fu Z, Linke S, et al. The asparaginyl hydroxylase factor inhibiting HIF-1alpha is an essential regulator of metabolism. Cell Metab 2010; 11(5): 364-78.
125. Woodward ER, Maher ER. Von Hippel-Lindau disease and endocrine tumour susceptibility. Endocr Relat Cancer 2006; 13(2): 415-25.
126. Chetty R, Kennedy M, Ezzat S, Asa SL. Pancreatic endocrine pathology in von Hippel-Lindau disease: an expanding spectrum of lesions. Endocr Pathol 2004; 15(2): 141-8.
127. Perigny M, Hammel P, Corcos O, et al. Pancreatic endocrine microadenomatosis in patients with von Hippel-Lindau disease: characterization by VHL/HIF pathway proteins expression. Am J Surg Pathol 2009; 33(5): 739-48.
128. Hammel PR, Vilgrain V, Terris B, et al. Pancreatic involvement in von Hippel-Lindau disease. The Groupe Francophone d'Etude de la Maladie de von Hippel-Lindau. Gastroenterology 2000; 119(4): 1087-95.
129. Rosen OM. After insulin binds. Science 1987; 237(4821): 1452-8.
130. Wertheimer E, Lu SP, Backeljauw PF, Davenport ML, Taylor SI. Homozygous deletion of the human insulin receptor gene results in leprechaunism. Nat Genet 1993; 5(1): 71-3.
131. Accili D, Drago J, Lee EJ, et al. Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nat Genet 1996; 12(1): 106-9.
132. Bruning JC, Michael MD, Winnay JN, et al. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 1998; 2(5): 559-69.
133. Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 1999; 96(3): 329-39.
134. Freeman H, Shimomura K, Horner E, Cox RD, Ashcroft FM. Nicotinamide nucleotide transhydrogenase: a key role in insulin secretion. Cell Metab 2006; 3(1): 35-45.
135. Toye AA, Lippiat JD, Proks P, et al. A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice. Diabetologia 2005; 48(4): 675-86.
136. Wong N, Blair AR, Morahan G, Andrikopoulos S. The deletion variant of nicotinamide nucleotide transhydrogenase (Nnt) does not affect insulin secretion or glucose tolerance. Endocrinology 2010; 151(1): 96-102.
137. Aston-Mourney K, Wong N, Kebede M, et al. Increased nicotinamide nucleotide transhydrogenase levels predispose to insulin hypersecretion in a mouse strain susceptible to diabetes. Diabetologia 2007; 50(12): 2476-85.
138. Garten A, Petzold S, Korner A, Imai S, Kiess W. Nampt: linking NAD biology, metabolism and cancer. Trends Endocrinol Metab 2009; 20(3): 130-8.
139. Revollo JR, Korner A, Mills KF, et al. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab 2007; 6(5): 363-75.
140. Guarente L, Picard F. Calorie restriction--the SIR2 connection. Cell 2005; 120(4): 473-82.
141. Bordone L, Motta MC, Picard F, et al. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. PLoS Biol 2006; 4(2): e31.
142. Moynihan KA, Grimm AA, Plueger MM, et al. Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice. Cell Metab 2005; 2(2): 105-17.
143. Ahuja N, Schwer B, Carobbio S, et al. Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. J Biol Chem 2007; 282(46): 33583-92.
144. Haigis MC, Mostoslavsky R, Haigis KM, et al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 2006; 126(5): 941-54.
145. Yechoor VK, Patti ME, Ueki K, et al. Distinct pathways of insulin-regulated versus diabetes-regulated gene expression: an in vivo analysis in MIRKO mice. Proc Natl Acad Sci USA 2004; 101(47): 16525-30.
146. Andrews ZB, Diano S, Horvath TL. Mitochondrial uncoupling proteins in the CNS: in support of function and survival. Nat Rev Neurosci 2005; 6(11): 829-40.
147. Klingenberg M, Echtay KS. Uncoupling proteins: the issues from a biochemist point of view. Biochim Biophys Acta 2001; 1504(1): 128-43.
148. Rousset S, Alves-Guerra MC, Mozo J, et al. The biology of mitochondrial uncoupling proteins. Diabetes 2004; 53 Suppl 1: S130-5.
149. Zhang CY, Baffy G, Perret P, et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 2001; 105(6): 745-55.
150. Produit-Zengaffinen N, Davis-Lameloise N, Perreten H, et al. Increasing uncoupling protein-2 in pancreatic beta cells does not alter glucose-induced insulin secretion but decreases production of reactive oxygen species. Diabetologia 2007; 50(1): 84-93.
151. Pi J, Bai Y, Daniel KW, et al. Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function. Endocrinology 2009; 150(7): 3040-8.
152. Steiner KE, Mouton SM, Bowles CR, Williams PE, Cherrington AD. The relative importance of first- and second- phase insulin secretion in countering the action of glucagon on glucose turnover in the conscious dog. Diabetes 1982; 31(11): 964-72.
153. Luzi L, DeFronzo RA. Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans. Am J Physiol 1989; 257(2 Pt 1): E241-6.
154. Mitrakou A, Kelley D, Mokan M, et al. Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. N Engl J Med 1992; 326(1): 22-9.
155. Briatore L, Salani B, Andraghetti G, et al. Restoration of acute insulin response in T2DM subjects 1 month after biliopancreatic diversion. Obesity (Silver Spring) 2008; 16(1): 77-81.
156. Long SD, O'Brien K, MacDonald KG, Jr., et al. Weight loss in severely obese subjects prevents the progression of impaired glucose tolerance to type II diabetes. A longitudinal interventional study. Diabetes Care 1994; 17(5): 372-5.
157. MacDonald KG, Jr., Long SD, Swanson MS, et al. The gastric bypass operation reduces the progression and mortality of non-insulin-dependent diabetes mellitus. J Gastrointest Surg 1997; 1(3): 213-20; discussion 20.
158. Polyzogopoulou EV, Kalfarentzos F, Vagenakis AG, Alexandrides TK. Restoration of euglycemia and normal acute insulin response to glucose in obese subjects with type 2 diabetes following bariatric surgery. Diabetes 2003; 52(5): 1098-103.
159. Hughes TA, Gwynne JT, Switzer BR, Herbst C, White G. Effects of caloric restriction and weight loss on glycemic control, insulin release and resistance, and atherosclerotic risk in obese patients with type II diabetes mellitus. Am J Med 1984; 77(1): 7-17.
160. Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011; 54(10): 2506-14.