Hyperinsulinism and Diabetes: Genetic Dissection of β Cell Metabolism-Excitation Coupling in Mice

Cell Metabolism

Volumn 10, Issue 6, 2009, Pages 442-453

  Remedi, Maria Sara ^a   Nichols, Colin G ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; CALCIUM CHANNEL L TYPE; CALCIUM ION; CALMODULIN; DIAZOXIDE; GLUCOKINASE; GLUCOSE; GLUCOSE TRANSPORTER; GLUCOSE TRANSPORTER 1; GLUCOSE TRANSPORTER 2; INSULIN; INWARDLY RECTIFYING POTASSIUM CHANNEL SUBUNIT KIR6.2; MITOCHONDRIAL PROTEIN; OXYGEN; POTASSIUM CHANNEL; POTASSIUM CHANNEL KCNQ1; PROTEIN KINASE C; SULFONYLUREA;

BIOLOGICAL MODEL; CELL ACTIVITY; CELL FUNCTION; CELL METABOLISM; CELL SECRETION; DIABETES MELLITUS; DRUG ACTIVITY; ENZYME ACTIVITY; GENE MUTATION; GENETIC MANIPULATION; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; GLYCEMIC CONTROL; HUMAN; HYPERGLYCEMIA; HYPERINSULINISM; INSULIN METABOLISM; INSULIN RELEASE; KNOCKOUT MOUSE; MATURITY ONSET DIABETES MELLITUS; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXYGEN CONSUMPTION; PANCREAS ISLET BETA CELL; PANCREAS ISLET DISEASE; PERMANENT NEONATAL DIABETES MELLITUS; PERSISTENT HYPERINSULINEMIC HYPOGLYCEMIA OF INFANCY; PHENOTYPE; POTASSIUM CURRENT; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN SYNTHESIS; REPOLARIZATION; REVIEW; SIGNAL TRANSDUCTION; STIMULUS SECRETION COUPLING; STREPTOZOCIN DIABETES;

ANIMALS; DIABETES MELLITUS; GLUCOSE; HUMANS; HYPERINSULINISM; INSULIN; INSULIN-SECRETING CELLS; ION CHANNELS; MICE; SIGNAL TRANSDUCTION;

ANIMALIA; MUS;

EID: 70449864125     PISSN: 15504131     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cmet.2009.10.011     Document Type: Review

References (180)

1. Aguilar-Bryan L., Bryan J., and Nakazaki M. Of mice and men: K(ATP) channels and insulin secretion. Recent Prog. Horm. Res. 56 (2001) 47-68
2. Araki E., Lipes M.A., Patti M.E., Bruning J.C., Haag III B., Johnson R.S., and Kahn C.R. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 372 (1994) 186-190
3. Arkblad E.L., Tuck S., Pestov N.B., Dmitriev R.I., Kostina M.B., Stenvall J., Tranberg M., and Rydstrom J. A Caenorhabditis elegans mutant lacking functional nicotinamide nucleotide transhydrogenase displays increased sensitivity to oxidative stress. Free Radic. Biol. Med. 38 (2005) 1518-1525
4. Arsenijevic D., Onuma H., Pecqueur C., Raimbault S., Manning B.S., Miroux B., Couplan E., Alves-Guerra M.C., Goubern M., Surwit R., et al. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat. Genet. 26 (2000) 435-439
5. Ashcroft F.M. From molecule to malady. Nature 440 (2006) 440-447
6. Ashcroft F.M., and Rorsman P. ATP-sensitive K+ channels: a link between B-cell metabolism and insulin secretion. Biochem. Soc. Trans. 18 (1990) 109-111
7. Atwater I., Rosario L., and Rojas E. Properties of the Ca-activated K+ channel in pancreatic beta-cells. Cell Calcium 4 (1983) 451-461
8. Aynsley-Green A. Nesidioblastosis of the pancreas in infancy. Dev. Med. Child Neurol. 23 (1981) 372-379
9. Bali D., Svetlanov A., Lee H.W., Fusco-DeMane D., Leiser M., Li B., Barzilai N., Surana M., Hou H., and Fleischer N. Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene. J. Biol. Chem. 270 (1995) 21464-21467
10. Barg S., Ma X., Eliasson L., Galvanovskis J., Gopel S.O., Obermuller S., Platzer J., Renstrom E., Trus M., Atlas D., et al. Fast exocytosis with few Ca(2+) channels in insulin-secreting mouse pancreatic B cells. Biophys. J. 81 (2001) 3308-3323
11. Bensch K.G., Mott J.L., Chang S.W., Hansen P.A., Moxley M.A., Chambers K.T., de Graaf W., Zassenhaus H.P., and Corbett J.A. Selective mtDNA mutation accumulation results in beta-cell apoptosis and diabetes development. Am. J. Physiol. Endocrinol. Metab. 296 (2009) E672-E680
12. Boini K.M., Graf D., Hennige A.M., Koka S., Kempe D.S., Wang K., Ackermann T.F., Foller M., Vallon V., Pfeifer K., et al. Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296 (2009) R1695-R1701
13. Braun M., Ramracheya R., Bengtsson M., Zhang Q., Karanauskaite J., Partridge C., Johnson P.R., and Rorsman P. Voltage-gated ion channels in human pancreatic beta-cells: electrophysiological characterization and role in insulin secretion. Diabetes 57 (2008) 1618-1628
14. Briaud I., Kelpe C.L., Johnson L.M., Tran P.O., and Poitout V. Differential effects of hyperlipidemia on insulin secretion in islets of langerhans from hyperglycemic versus normoglycemic rats. Diabetes 51 (2002) 662-668
15. Cantley J., Selman C., Shukla D., Abramov A.Y., Forstreuter F., Esteban M.A., Claret M., Lingard S.J., Clements M., Harten S.K., et al. Deletion of the von Hippel-Lindau gene in pancreatic beta cells impairs glucose homeostasis in mice. J. Clin. Invest. 119 (2009) 125-135
16. Cauchi S., Meyre D., Durand E., Proença C., Marre M., Hadjadj S., Choquet H., De Graeve F., Gaget S., Allegaert F., et al. Post genome-wide association studies of novel genes associated with type 2 diabetes show gene-gene interaction and high predictive value. PLoS ONE 3 (2008) e2031
17. Chan C.B., MacDonald P.E., Saleh M.C., Johns D.C., Marban E., and Wheeler M.B. Overexpression of uncoupling protein 2 inhibits glucose-stimulated insulin secretion from rat islets. Diabetes 48 (1999) 1482-1486
18. Chan C.B., De Leo D., Joseph J.W., McQuaid T.S., Ha X.F., Xu F., Tsushima R.G., Pennefather P.S., Salapatek A.M., and Wheeler M.B. Increased uncoupling protein-2 levels in beta-cells are associated with impaired glucose-stimulated insulin secretion: mechanism of action. Diabetes 50 (2001) 1302-1310
19. Chistiakov D.A., Potapov V.A., Khodirev D.C., Shamkhalova M.S., Shestakova M.V., and Nosikov V.V. Genetic variations in the pancreatic ATP-sensitive potassium channel, beta-cell dysfunction, and susceptibility to type 2 diabetes. Acta Diabetol. 46 (2009) 43-49
20. Clement IV J.P., Kunjilwar K., Gonzalez G., Schwanstecher M., Panten U., Aguilar-Bryan L., and Bryan J. Association and stoichiometry of K(ATP) channel subunits. Neuron 18 (1997) 827-838
21. Codner E., Deng L., Perez-Bravo F., Roman R., Lanzano P., Cassorla F., and Chung W.K. Glucokinase mutations in young children with hyperglycemia. Diabetes Metab. Res. Rev. 22 (2006) 348-355
22. Cuesta-Munoz A.L., Huopio H., Otonkoski T., Gomez-Zumaquero J.M., Nanto-Salonen K., Rahier J., Lopez-Enriquez S., Garcia-Gimeno M.A., Sanz P., Soriguer F.C., and Laakso M. Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation. Diabetes 53 (2004) 2164-2168
23. Daniel S., Noda M., Straub S.G., and Sharp G.W. Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion. Diabetes 48 (1999) 1686-1690
24. de Lonlay P., Fournet J.C., Touati G., Groos M.S., Martin D., Sevin C., Delagne V., Mayaud C., Chigot V., Sempoux C., et al. Heterogeneity of persistent hyperinsulinaemic hypoglycaemia. A series of 175 cases. Eur. J. Pediatr. 161 (2002) 37-48
25. Del Prato S., Bianchi C., and Marchetti P. beta-cell function and anti-diabetic pharmacotherapy. Diabetes Metab. Res. Rev. 23 (2007) 518-527
26. Dufer M., Haspel D., Krippeit-Drews P., Aguilar-Bryan L., Bryan J., and Drews G. Oscillations of membrane potential and cytosolic Ca(2+) concentration in SUR1(-/-) beta cells. Diabetologia 47 (2004) 488-498
27. Dukes I.D., and Philipson L.H. K+ channels: generating excitement in pancreatic beta-cells. Diabetes 45 (1996) 845-853
28. Dunne M.J., Kane C., Shepherd R.M., Sanchez J.A., James R.F., Johnson P.R., Aynsley-Green A., Lu S., Clement IV J.P., Lindley K.J., Seino S., and Aguilar-Bryan L. Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor. N. Engl. J. Med. 336 (1997) 703-706
29. Dunne M.J., Cosgrove K.E., Shepherd R.M., Aynley-Green A., and Lindley K.J. Hyperinsulinism in Infancy: From Basic Science to Clinical Disease. Physiol. Rev. 84 (2004) 239-275
30. Easom R.A. CaM kinase II: a protein kinase with extraordinary talents germane to insulin exocytosis. Diabetes 48 (1999) 675-684
31. Echtay K.S., Roussel D., St-Pierre J., Jekabsons M.B., Cadenas S., Stuart J.A., Harper J.A., Roebuck S.J., Morrison A., Pickering S., et al. Superoxide activates mitochondrial uncoupling proteins. Nature 415 (2002) 96-99
32. Efrat S., Tal M., and Lodish H.F. The pancreatic beta-cell glucose sensor. Trends Biochem. Sci. 19 (1994) 535-538
33. Epstein P.N., Boschero A.C., Atwater I., Cai X., and Overbeek P.A. Expression of yeast hexokinase in pancreatic beta cells of transgenic mice reduces blood glucose, enhances insulin secretion, and decreases diabetes. Proc. Natl. Acad. Sci. USA 89 (1992) 12038-12042
34. Epstein P.N., Ribar T.J., Decker G.L., Yaney G., and Means A.R. Elevated beta-cell calmodulin produces a unique insulin secretory defect in transgenic mice. Endocrinology 130 (1992) 1387-1393
35. Erecinska M., Bryla J., Michalik M., Meglasson M.D., and Nelson D. Energy metabolism in islets of Langerhans. Biochim. Biophys. Acta 1101 (1992) 273-295
36. Fajans S.S., Bell G.I., and Polonsky K.S. Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N. Engl. J. Med. 345 (2001) 971-980
37. Florez J.C., Burtt N., de Bakker P.I., Almgren P., Tuomi T., Holmkvist J., Gaudet D., Hudson T.J., Schaffner S.F., Daly M.J., et al. Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region. Diabetes 53 (2004) 1360-1368
38. Freeman H., Shimomura K., Cox R.D., and Ashcroft F.M. Nicotinamide nucleotide transhydrogenase: a link between insulin secretion, glucose metabolism and oxidative stress. Biochem. Soc. Trans. 34 (2006) 806-810
39. Girard C.A., Wunderlich F.T., Shimomura K., Collins S., Kaizik S., Proks P., Abdulkader F., Clark A., Ball V., Zubcevic L., et al. Expression of an activating mutation in the gene encoding the KATP channel subunit Kir6.2 in mouse pancreatic beta cells recapitulates neonatal diabetes. J. Clin. Invest. 119 (2009) 80-90
40. Gloyn A.L. Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy. Hum. Mutat. 22 (2003) 353-362
41. Gloyn A.L. The search for type 2 diabetes genes. Ageing Res. Rev. 2 (2003) 111-127
42. Gloyn A.L., Ellard S., Shield J.P., Temple I.K., Mackay D.J., Polak M., Barrett T., and Hattersley A.T. Complete glucokinase deficiency is not a common cause of permanent neonatal diabetes. Diabetologia 45 (2002) 290
43. Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., et al. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N. Engl. J. Med. 350 (2004) 1838-1849
44. Grill V., and Bjorklund A. Overstimulation and beta-cell function. Diabetes 50 Suppl 1 (2001) S122-S124
45. Grimberg A., Ferry Jr. R.J., Kelly A., Koo-McCoy S., Polonsky K., Glaser B., Permutt M.A., Aguilar-Bryan L., Stafford D., Thornton P.S., et al. Dysregulation of insulin secretion in children with congenital hyperinsulinism due to sulfonylurea receptor mutations. Diabetes 50 (2001) 322-328
46. Grupe A., Hultgren B., Ryan A., Ma Y.H., Bauer M., and Stewart T.A. Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis. Cell 83 (1995) 69-78
47. Guillam M.T., Hummler E., Schaerer E., Yeh J.I., Birnbaum M.J., Beermann F., Schmidt A., Deriaz N., Thorens B., and Wu J.Y. Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nat. Genet. 17 (1997) 327-330
48. Guillam M.T., Dupraz P., and Thorens B. Glucose uptake, utilization, and signaling in GLUT2-null islets. Diabetes 49 (2000) 1485-1491
49. Guillausseau P.J., Meas T., Virally M., Laloi-Michelin M., Medeau V., and Kevorkian J.P. Abnormalities in insulin secretion in type 2 diabetes mellitus. Diabetes Metab. 34 Suppl 2 (2008) S43-S48
50. Guldstrand M., Grill V., Bjorklund A., Lins P.E., and Adamson U. Improved beta cell function after short-term treatment with diazoxide in obese subjects with type 2 diabetes. Diabetes Metab. 28 (2002) 448-456
51. Hattersley A.T., and Ashcroft F.M. Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy. Diabetes 54 (2005) 2503-2513
52. Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., and Stanley C.A. Genotype-Phenotype Correlations in Children with Congenital Hyperinsulinism Due to Recessive Mutations of the Adenosine Triphosphate-Sensitive Potassium Channel Genes. J. Clin. Endocrinol. Metab. 90 (2005) 789-794
53. Herrera P.L. Defining the cell lineages of the islets of Langerhans using transgenic mice. Int. J. Dev. Biol. 46 (2002) 97-103
54. Himms-Hagen J., and Harper M.E. Physiological role of UCP3 may be export of fatty acids from mitochondria when fatty acid oxidation predominates: an hypothesis. Exp. Biol. Med. 226 (2001) 78-84
55. Hiramatsu S., Hoog A., Moller C., and Grill V. Treatment with diazoxide causes prolonged improvement of beta-cell function in rat islets transplanted to a diabetic environment. Metabolism 49 (2000) 657-661
56. Hoek J.B., and Rydstrom J. Physiological roles of nicotinamide nucleotide transhydrogenase. Biochem. J. 254 (1988) 1-10
57. Hofmann F., Illes P., Aktories K., and Meyer D.K. Voltage-dependent calcium channels: from structure to function. Br. J. Pharmacol. 127 (1999) 1060-1063
58. Holmkvist J., Tojjar D., Almgren P., Lyssenko V., Lindgren C.M., Isomaa B., Tuomi T., Berglund G., Renstrom E., and Groop L. Polymorphisms in the gene encoding the voltage-dependent Ca(2+) channel Ca (V)2.3 (CACNA1E) are associated with type 2 diabetes and impaired insulin secretion. Diabetologia 50 (2007) 2467-2475
59. Hu C., Wang C., Zhang R., Ma X., Wang J., Lu J., Qin W., Bao Y., Xiang K., and Jia W. Variations in KCNQ1 are associated with type 2 diabetes and beta cell function in a Chinese population. Diabetologia 52 (2009) 1322-1325
60. Hubinont C.J., Best L., Sener A., and Malaisse W.J. Activation of protein kinase C by a tumor-promoting phorbol ester in pancreatic islets. FEBS Lett. 170 (1984) 247-253
61. Huopio H., Shyng S.L., Otonkoski T., and Nichols C.G. K(ATP) channels and insulin secretion disorders. Am. J. Physiol. Endocrinol. Metab. 283 (2002) E207-E216
62. Huopio H., Vauhkonen I., Komulainen J., Niskanen L., Otonkoski T., and Laakso M. Carriers of an inactivating beta-cell ATP-sensitive K(+) channel mutation have normal glucose tolerance and insulin sensitivity and appropriate insulin secretion. Diabetes Care 25 (2002) 101-106
63. Ichii H., Inverardi L., Pileggi A., Molano R.D., Cabrera O., Caicedo A., Messinger S., Kuroda Y., Berggren P.O., and Ricordi C. A novel method for the assessment of cellular composition and beta-cell viability in human islet preparations. Am. J. Transplant. 5 (2005) 1635-1645
64. Inagaki N., Gonoi T., Clement J.P., Namba N., Inazawa J., Gonzalez G., Aguilar-Bryan L., Seino S., and Bryan J. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science 270 (1995) 1166-1170
65. Iwashima Y., Pugh W., Depaoli A.M., Takeda J., Seino S., Bell G.I., and Polonsky K.S. Expression of calcium channel mRNAs in rat pancreatic islets and downregulation after glucose infusion. Diabetes 42 (1993) 948-955
66. Jacobson D.A., Kuznetsov A., Lopez J.P., Kash S., Ammala C.E., and Philipson L.H. Kv2.1 ablation alters glucose-induced islet electrical activity, enhancing insulin secretion. Cell Metab. 6 (2007) 229-235
67. Jing X., Li D., Olofsson C.S., Salehi A., Surve V.V., Caballero J., Ivarsson R., Lundquist I., Pereverzev A., Schneider T., et al. CaV2.3 calcium channels control second-phase insulin release. J. Clin. Invest. 115 (2005) 146-154
68. Jonsson A., Isomaa B., Tuomi T., Taneera J., Salehi A., Nilsson P., Groop L., and Lyssenko V. A variant in the KCNQ1 gene predicts future type 2 diabetes and mediates impaired insulin secretion. Diabetes 58 (2009) 2409-2413
69. Joseph J.W., Koshkin V., Zhang C.Y., Wang J., Lowell B.B., Chan C.B., and Wheeler M.B. Uncoupling protein 2 knockout mice have enhanced insulin secretory capacity after a high-fat diet. Diabetes 51 (2002) 3211-3219
70. Kane C., Shepherd R.M., Squires P.E., Johnson P.R., James R.F., Milla P.J., Aynsley-Green A., Lindley K.J., and Dunne M.J. Loss of functional KATP channels in pancreatic beta-cells causes persistent hyperinsulinemic hypoglycemia of infancy. Nat. Med. 2 (1996) 1344-1347
71. Kang Y., Huang X., Pasyk E.A., Ji J., Holz G.G., Wheeler M.B., Tsushima R.G., and Gaisano H.Y. Syntaxin-3 and syntaxin-1A inhibit L-type calcium channel activity, insulin biosynthesis and exocytosis in beta-cell lines. Diabetologia 45 (2002) 231-241
72. Kassis N., Bernard C., Pusterla A., Casteilla L., Penicaud L., Richard D., Ricquier D., and Ktorza A. Correlation between pancreatic islet uncoupling protein-2 (UCP2) mRNA concentration and insulin status in rats. Int. J. Exp. Diabetes Res. 1 (2000) 185-193
73. Katagiri H., Asano T., Ishihara H., Inukai K., Anai M., Miyazaki J., Tsukuda K., Kikuchi M., Yazaki Y., and Oka Y. Nonsense mutation of glucokinase gene in late-onset non-insulin-dependent diabetes mellitus. Lancet 340 (1992) 1316-1317
74. Koster J.C., Marshall B.A., Ensor N., Corbett J.A., and Nichols C.G. Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes. Cell 100 (2000) 645-654
75. Koster J.C., Remedi M.S., Flagg T.P., Johnson J.D., Markova K.P., Marshall B.A., and Nichols C.G. Hyperinsulinism induced by targeted suppression of beta cell KATP channels. Proc. Natl. Acad. Sci. USA 99 (2002) 16992-16997
76. Koster J.C., Remedi M.S., Masia R., Patton B., Tong A., and Nichols C.G. Expression of ATP-insensitive KATP channels in pancreatic beta-cells underlies a spectrum of diabetic phenotypes. Diabetes 55 (2006) 2957-2964
77. Krauss S., Zhang C.-Y., Scorrano L., Dalgaard L.T., St-Pierre J., Grey S.T., and Lowell B.B. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic {beta} cell dysfunction. J. Clin. Invest. 112 (2003) 1831-1842
78. Lam P.P., Leung Y.M., Sheu L., Ellis J., Tsushima R.G., Osborne L.R., and Gaisano H.Y. Transgenic mouse overexpressing syntaxin-1A as a diabetes model. Diabetes 54 (2005) 2744-2754
79. Lee M.P., Hu R.J., Johnson L.A., and Feinberg A.P. Human KVLQT1 gene shows tissue-specific imprinting and encompasses Beckwith-Wiedemann syndrome chromosomal rearrangements. Nat. Genet. 15 (1997) 181-185
80. Leibowitz G., Glaser B., Higazi A.A., Salameh M., Cerasi E., and Landau H. Hyperinsulinemic hypoglycemia of infancy (nesidioblastosis) in clinical remission: high incidence of diabetes mellitus and persistent beta-cell dysfunction at long-term follow-up. J. Clin. Endocrinol. Metab. 80 (1995) 386-392
81. Leung Y.M., Kang Y., Gao X., Xia F., Xie H., Sheu L., Tsuk S., Lotan I., Tsushima R.G., and Gaisano H.Y. Syntaxin 1A binds to the cytoplasmic C terminus of Kv2.1 to regulate channel gating and trafficking. J. Biol. Chem. 278 (2003) 17532-17538
82. Leung Y.M., Kang Y., Xia F., Sheu L., Gao X., Xie H., Tsushima R.G., and Gaisano H.Y. Open form of syntaxin-1A is a more potent inhibitor than wild-type syntaxin-1A of Kv2.1 channels. Biochem. J. 387 (2005) 195-202
83. Lin Y.-W., MacMullen C., Ganguly A., Stanley C.A., and Shyng S.-L. A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels. J. Biol. Chem. 281 (2006) 3006-3012
84. Maassen J.A. Mitochondrial diabetes: pathophysiology, clinical presentation, and genetic analysis. Am. J. Med. Genet. 115 (2002) 66-70
85. Maassen J.A., 'T Hart L.M., Van Essen E., Heine R.J., Nijpels G., Jahangir Tafrechi R.S., Raap A.K., Janssen G.M., and Lemkes H.H. Mitochondrial diabetes: molecular mechanisms and clinical presentation. Diabetes 53 (2004) S103-S109
86. MacDonald P.E., Ha X.F., Wang J., Smukler S.R., Sun A.M., Gaisano H.Y., Salapatek A.M., Backx P.H., and Wheeler M.B. Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion. Mol. Endocrinol. 15 (2001) 1423-1435
87. MacDonald P.E., Sewing S., Wang J., Joseph J.W., Smukler S.R., Sakellaropoulos G., Saleh M.C., Chan C.B., Tsushima R.G., Salapatek A.M., and Wheeler M.B. Inhibition of Kv2.1 voltage-dependent K+ channels in pancreatic beta-cells enhances glucose-dependent insulin secretion. J. Biol. Chem. 277 (2002) 44938-44945
88. MacDonald P.E., Joseph J.W., and Rorsman P. Glucose-sensing mechanisms in pancreatic beta-cells. Philos. Trans. R. Soc. Lond. B Biol. Sci. 360 (2005) 2211-2225
89. Maechler P., and Wollheim C.B. Mitochondrial function in normal and diabetic beta-cells. Nature 414 (2001) 807-812
90. Matschinsky F.M. Banting Lecture 1995. A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabetes 45 (1996) 223-241
91. Matveyenko A.V., and Butler P.C. Relationship between beta-cell mass and diabetes onset. Diabetes Obes. Metab. 10 Suppl 4 (2008) 23-31
92. Mazor-Aronovitch K., Landau H., and Gillis D. Surgical versus non-surgical treatment of congenital hyperinsulinism. Pediatr. Endocrinol. Rev. 6 (2009) 424-430
93. McCarthy M.I. Casting a wider net for diabetes susceptibility genes. Nat. Genet. 40 (2008) 1039-1040
94. Mears D. Regulation of insulin secretion in islets of Langerhans by Ca(2+)channels. J. Membr. Biol. 200 (2004) 57-66
95. Miki T., Tashiro F., Iwanaga T., Nagashima K., Yoshitomi H., Aihara H., Nitta Y., Gonoi T., Inagaki N., Miyazaki J., and Seino S. Abnormalities of pancreatic islets by targeted expression of a dominant-negative KATP channel. Proc. Natl. Acad. Sci. USA 94 (1997) 11969-11973
96. Miki T., Nagashima K., Tashiro F., Kotake K., Yoshitomi H., Tamamoto A., Gonoi T., Iwanaga T., Miyazaki J., and Seino S. Defective insulin secretion and enhanced insulin action in KATP channel- deficient mice. Proc. Natl. Acad. Sci. USA 95 (1998) 10402-10406
97. Minami K., Yokokura M., Ishizuka N., and Seino S. Normalization of Intracellular Ca2+ Induces a Glucose-responsive State in Glucose-unresponsive beta -Cells. J. Biol. Chem. 277 (2002) 25277-25282
98. Mussig K., Staiger H., Machicao F., Kirchhoff K., Guthoff M., Schafer S.A., Kantartzis K., Silbernagel G., Stefan N., Holst J.J., et al. Association of type 2 diabetes candidate polymorphisms in KCNQ1 with incretin and insulin secretion. Diabetes 58 (2009) 1715-1720
99. Nestorowicz A., Glaser B., Wilson B.A., Shyng S.L., Nichols C.G., Stanley C.A., Thornton P.S., and Permutt M.A. Genetic heterogeneity in familial hyperinsulinism. Hum. Mol. Genet. 7 (1998) 1119-1128
100. Nichols C.G. KATP channels as molecular sensors of cellular metabolism. Nature 440 (2006) 470-476
101. Nichols C.G., and Koster J.C. Diabetes and insulin secretion: whither KATP?. Am. J. Physiol. Endocrinol. Metab. 283 (2002) E403-E412
102. Nichols C.G., Shyng S.L., Nestorowicz A., Glaser B., Clement J.P., Gonzalez G., Aguilarbryan L., Permutt M.A., and Bryan J. Adenosine Diphosphate As an Intracellular Regulator Of Insulin Secretion. Science 272 (1996) 1785-1787
103. Nichols C.G., Koster J.C., and Remedi M.S. beta-cell hyperexcitability: from hyperinsulinism to diabetes. Diabetes Obes. Metab. 9 Suppl 2 (2007) 81-88
104. Nielsen E.M., Hansen L., Carstensen B., Echwald S.M., Drivsholm T., Glumer C., Thorsteinsson B., Borch-Johnsen K., Hansen T., and Pedersen O. The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. Diabetes 52 (2003) 573-577
105. Nishikawa T., Edelstein D., Du X.L., Yamagishi S., Matsumura T., Kaneda Y., Yorek M.A., Beebe D., Oates P.J., Hammes H.P., et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404 (2000) 787-790
106. Njolstad P.R., Sovik O., Cuesta-Munoz A., Bjorkhaug L., Massa O., Barbetti F., Undlien D.E., Shiota C., Magnuson M.A., Molven A., et al. Neonatal diabetes mellitus due to complete glucokinase deficiency. N. Engl. J. Med. 344 (2001) 1588-1592
107. Njolstad P.R., Sagen J.V., Bjorkhaug L., Odili S., Shehadeh N., Bakry D., Sarici S.U., Alpay F., Molnes J., Molven A., et al. Permanent neonatal diabetes caused by glucokinase deficiency: inborn error of the glucose-insulin signaling pathway. Diabetes 52 (2003) 2854-2860
108. Oyama K., Minami K., Ishizaki K., Fuse M., Miki T., and Seino S. Spontaneous recovery from hyperglycemia by regeneration of pancreatic beta-cells in Kir6.2G132S transgenic mice. Diabetes 55 (2006) 1930-1938
109. Page R., Hattersley A., and Turner R. Beta-cell secretory defect caused by mutations in glucokinase gene. Lancet 340 (1992) 1162-1163
110. Palladino A.A., Bennett M.J., and Stanley C.A. Hyperinsulinism in infancy and childhood: when an insulin level is not always enough. Clin. Chem. 54 (2008) 256-263
111. Pascoe L., Frayling T.M., Weedon M.N., Mari A., Tura A., Ferrannini E., and Walker M. Beta cell glucose sensitivity is decreased by 39% in non-diabetic individuals carrying multiple diabetes-risk alleles compared with those with no risk alleles. Diabetologia 51 (2008) 1989-1992
112. Pearson E.R., Flechtner I., Njolstad P.R., Malecki M.T., Flanagan S.E., Larkin B., Ashcroft F.M., Klimes I., Codner E., Iotova V., et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N. Engl. J. Med. 355 (2006) 467-477
113. Pereverzev A., Mikhna M., Vajna R., Gissel C., Henry M., Weiergraber M., Hescheler J., Smyth N., and Schneider T. Disturbances in glucose-tolerance, insulin-release, and stress-induced hyperglycemia upon disruption of the Ca(v)2.3 (alpha 1E) subunit of voltage-gated Ca(2+) channels. Mol. Endocrinol. 16 (2002) 884-895
114. Pertusa J.A., Sanchez-Andres J.V., Martin F., and Soria B. Effects of calcium buffering on glucose-induced insulin release in mouse pancreatic islets: an approximation to the calcium sensor. J. Physiol. 520 (1999) 473-483
115. Pfutzner A., Lorra B., Abdollahnia M.R., Kann P.H., Mathieu D., Pehnert C., Oligschleger C., Kaiser M., and Forst T. The switch from sulfonylurea to preprandial short- acting insulin analog substitution has an immediate and comprehensive beta-cell protective effect in patients with type 2 diabetes mellitus. Diabetes Technol. Ther. 8 (2006) 375-384
116. Philipson L.H. Beta-cell ion channels: keys to endodermal excitability. Horm. Metab. Res. 31 (1999) 455-461
117. Philipson L.H., Rosenberg M.P., Kuznetsov A., Lancaster M.E., Worley III J.F., Roe M.W., and Dukes I.D. Delayed rectifier K+ channel overexpression in transgenic islets and beta-cells associated with impaired glucose responsiveness. J. Biol. Chem. 269 (1994) 27787-27790
118. Platzer J., Engel J., Schrott-Fischer A., Stephan K., Bova S., Chen H., Zheng H., and Striessnig J. Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels. Cell 102 (2000) 89-97
119. Poitout V., and Robertson R.P. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr. Rev. 29 (2008) 351-366
120. Porter J.R., Shaw N.J., Barrett T.G., Hattersley A.T., Ellard S., and Gloyn A.L. Permanent neonatal diabetes in an Asian infant. J. Pediatr. 146 (2005) 131-133
121. Prentki M., and Matschinsky F.M. Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion. Physiol. Rev. 67 (1987) 1185-1248
122. Remedi M.S., and Nichols C.G. Chronic antidiabetic sulfonylureas in vivo: reversible effects on mouse pancreatic beta-cells. PLoS Med. 5 (2008) e206
123. Remedi M.S., Koster J.C., Patton B.L., and Nichols C.G. ATP-Sensitive K+ Channel Signaling in Glucokinase-Deficient Diabetes. Diabetes 54 (2005) 2925-2931
124. Remedi M.S., Rocheleau J.V., Tong A., Patton B.L., McDaniel M.L., Piston D.W., Koster J.C., and Nichols C.G. Hyperinsulinism in mice with heterozygous loss of K(ATP) channels. Diabetologia 49 (2006) 2368-2378
125. Remedi M.S., Kurata H.T., Scott A., Wunderlich F.T., Rother E., Kleinridders A., Tong A., Bruning J.C., Koster J.C., and Nichols C.G. Secondary consequences of beta cell inexcitability: identification and prevention in a murine model of K(ATP)-induced neonatal diabetes mellitus. Cell Metab. 9 (2009) 140-151
126. Ribar T.J., Epstein P.N., Overbeek P.A., and Means A.R. Targeted overexpression of an inactive calmodulin that binds Ca2+ to the mouse pancreatic beta-cell results in impaired secretion and chronic hyperglycemia. Endocrinology 136 (1995) 106-115
127. Richardson C.C., Hussain K., Jones P.M., Persaud S., Lobner K., Boehm A., Clark A., and Christie M.R. Low levels of glucose transporters and K+ATP channels in human pancreatic beta cells early in development. Diabetologia 50 (2007) 1000-1005
128. Riedel M.J., Boora P., Steckley D., de Vries G., and Light P.E. Kir6.2 polymorphisms sensitize beta-cell ATP-sensitive potassium channels to activation by acyl CoAs: a possible cellular mechanism for increased susceptibility to type 2 diabetes?. Diabetes 52 (2003) 2630-2635
129. Roe M.W., Worley III J.F., Mittal A.A., Kuznetsov A., DasGupta S., Mertz R.J., Witherspoon III S.M., Blair N., Lancaster M.E., McIntyre M.S., et al. Expression and function of pancreatic beta-cell delayed rectifier K+ channels. Role in stimulus-secretion coupling. J. Biol. Chem. 271 (1996) 32241-32246
130. Rorsman P., and Trube G. Calcium and delayed potassium currents in mouse pancreatic beta-cells under voltage-clamp conditions. J. Physiol. 374 (1986) 531-550
131. Rustenbeck I. Desensitization of insulin secretion. Biochem. Pharmacol. 63 (2002) 1921-1935
132. Sako Y., and Grill V.E. A 48-hour lipid infusion in the rat time-dependently inhibits glucose- induced insulin secretion and B cell oxidation through a process likely coupled to fatty acid oxidation. Endocrinology 127 (1990) 1580-1589
133. Sakura H., Bond C., Warren-Perry M., Horsley S., Kearney L., Tucker S., Adelman J., Turner R., and Ashcroft F.M. Characterization and variation of a human inwardly-rectifying-K-channel gene (KCNJ6): a putative ATP-sensitive K-channel subunit. FEBS Lett. 367 (1995) 193-197
134. Sakura H., Wat N., Horton V., Millns H., Turner R.C., and Ashcroft F.M. Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in while Caucasian subjects or evidence of abnormal function when expressed in vitro. Diabetologia 39 (1996) 1233-1236
135. Sakura H., Ashcroft S.J., Terauchi Y., Kadowaki T., and Ashcroft F.M. Glucose modulation of ATP-sensitive K-currents in wild-type, homozygous and heterozygous glucokinase knock-out mice. Diabetologia 41 (1998) 654-659
136. Samec S., Seydoux J., and Dulloo A.G. Role of UCP homologues in skeletal muscles and brown adipose tissue: mediators of thermogenesis or regulators of lipids as fuel substrate?. FASEB J. 12 (1998) 715-724
137. Sargsyan E., Ortsater H., Thorn K., and Bergsten P. Diazoxide-induced beta-cell rest reduces endoplasmic reticulum stress in lipotoxic beta-cells. J. Endocrinol. 199 (2008) 41-50
138. Saxena R., Voight B.F., Lyssenko V., Burtt N.P., de Bakker P.I., Chen H., Roix J.J., Kathiresan S., Hirschhorn J.N., Daly M.J., et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316 (2007) 1331-1336
139. Schulla V., Renstrom E., Feil R., Feil S., Franklin I., Gjinovci A., Jing X.J., Laux D., Lundquist I., Magnuson M.A., et al. Impaired insulin secretion and glucose tolerance in beta cell-selective Ca(v)1.2 Ca2+ channel null mice. EMBO J. 22 (2003) 3844-3854
140. Schwanstecher C., Meyer U., and Schwanstecher M. K(IR)6.2 polymorphism predisposes to type 2 diabetes by inducing overactivity of pancreatic beta-cell ATP-sensitive K(+) channels. Diabetes 51 (2002) 875-879
141. Seghers V., Nakazaki M., DeMayo F., Aguilar-Bryan L., and Bryan J. Sur1 knockout mice. A model for K(ATP) channel-independent regulation of insulin secretion. J. Biol. Chem. 275 (2000) 9270-9277
142. Seisenberger C., Specht V., Welling A., Platzer J., Pfeifer A., Kuhbandner S., Striessnig J., Klugbauer N., Feil R., and Hofmann F. Functional embryonic cardiomyocytes after disruption of the L-type alpha1C (Cav1.2) calcium channel gene in the mouse. J. Biol. Chem. 275 (2000) 39193-39199
143. Shehadeh N., Bakri D., Njolstad P.R., and Gershoni-Baruch R. Clinical characteristics of mutation carriers in a large family with glucokinase diabetes (MODY2). Diabet. Med. 22 (2005) 994-998
144. Shiota M., Postic C., Fujimoto Y., Jetton T.L., Dixon K., Pan D., Grimsby J., Grippo J.F., Magnuson M.A., and Cherrington A.D. Glucokinase gene locus transgenic mice are resistant to the development of obesity-induced type 2 diabetes. Diabetes 50 (2001) 622-629
145. Shiota C., Larsson O., Shelton K.D., Shiota M., Efanov A.M., Hoy M., Lindner J., Kooptiwut S., Juntti-Berggren L., Gromada J., et al. Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose. J. Biol. Chem. 277 (2002) 37176-37183
146. Shyng S., and Nichols C.G. Octameric stoichiometry of the KATP channel complex. J. Gen. Physiol. 110 (1997) 655-664
147. Shyng S.L., Ferrigni T., Shepard J.B., Nestorowicz A., Glaser B., Permutt M.A., and Nichols C.G. Functional analyses of novel mutations in the sulfonylurea receptor 1 associated with persistent hyperinsulinemic hypoglycemia of infancy. Diabetes 47 (1998) 1145-1151
148. Silva J.P., Kohler M., Graff C., Oldfors A., Magnuson M.A., Berggren P.O., and Larsson N.G. Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes. Nat. Genet. 26 (2000) 336-340
149. Sivaprasadarao A., Taneja T.K., Mankouri J., and Smith A.J. Trafficking of ATP-sensitive potassium channels in health and disease. Biochem. Soc. Trans. 35 (2007) 1055-1059
150. Sladek R., Rocheleau G., Rung J., Dina C., Shen L., Serre D., Boutin P., Vincent D., Belisle A., Hadjadj S., et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445 (2007) 881-885
151. Smilinich N.J., Day C.D., Fitzpatrick G.V., Caldwell G.M., Lossie A.C., Cooper P.R., Smallwood A.C., Joyce J.A., Schofield P.N., Reik W., et al. A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome. Proc. Natl. Acad. Sci. USA 96 (1999) 8064-8069
152. Smith A.J., Taneja T.K., Mankouri J., and Sivaprasadarao A. Molecular cell biology of KATP channels: implications for neonatal diabetes. Expert Rev. Mol. Med. 9 (2007) 1-17
153. Splawski I., Timothy K.W., Sharpe L.M., Decher N., Kumar P., Bloise R., Napolitano C., Schwartz P.J., Joseph R.M., Condouris K., et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 119 (2004) 19-31
154. Sreenan S., Cockburn B., Baldwin A., Ostrega D., Levisetti M., Grupe A., Bell G., Stewart T., Roe M., and Polonsky K. Adaptation to hyperglycemia enhances insulin secretion in glucokinase mutant mice. Diabetes 47 (1998) 1881-1888
155. Stancakova A., Kuulasmaa T., Paananen J., Jackson A.U., Bonnycastle L.L., Collins F.S., Boehnke M., Kuusisto J., and Laakso M. Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men. Diabetes 58 (2009) 2129-2136
156. Stanley C.A. Advances in Diagnosis and Treatment of Hyperinsulinism in Infants and Children. J. Clin. Endocrinol. Metab. 87 (2002) 4857-4859
157. Su J., Yu H., Lenka N., Hescheler J., and Ullrich S. The expression and regulation of depolarization-activated K+ channels in the insulin-secreting cell line INS-1. Pflugers Archiv - European. J. Physiol. 442 (2001) 49-56
158. Sugden M.C., Christie M.R., and Ashcroft S.J. Presence and possible role of calcium-dependent regulator (calmodulin) in rat islets of Langerhans. FEBS Lett. 105 (1979) 95-100
159. Tamarina N.A., Wang Y., Mariotto L., Kuznetsov A., Bond C., Adelman J., and Philipson L.H. Small-conductance calcium-activated K+ channels are expressed in pancreatic islets and regulate glucose responses. Diabetes 52 (2003) 2000-2006
160. Tamemoto H., Kadowaki T., Tobe K., Yagi T., Sakura H., Hayakawa T., Terauchi Y., Ueki K., Kaburagi Y., Satoh S., et al. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature 372 (1994) 182-186
161. Tan J.T., Nurbaya S., Gardner D., Ye S., Tai E.S., and Ng D.P. Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore. Diabetes 58 (2009) 1445-1449
162. Terauchi Y., Sakura H., Yasuda K., Iwamoto K., Takahashi N., Ito K., Kasai H., Suzuki H., Ueda O., Kamada N., et al. Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes mellitus due to defective insulin secretion to glucose. J. Biol. Chem. 270 (1995) 30253-30256
163. Terauchi Y., Iwamoto K., Tamemoto H., Komeda K., Ishii C., Kanazawa Y., Asanuma N., Aizawa T., Akanuma Y., Yasuda K., et al. Development of non-insulin-dependent diabetes mellitus in the double knockout mice with disruption of insulin receptor substrate-1 and beta cell glucokinase genes. Genetic reconstitution of diabetes as a polygenic disease. J. Clin. Invest. 99 (1997) 861-866
164. Thorens B. GLUT2 in pancreatic and extra-pancreatic gluco-detection. Mol. Membr. Biol. 18 (2001) 265-273
165. Thorens B., Guillam M.T., Beermann F., Burcelin R., and Jaquet M. Transgenic reexpression of GLUT1 or GLUT2 in pancreatic beta cells rescues GLUT2-null mice from early death and restores normal glucose- stimulated insulin secretion. J. Biol. Chem. 275 (2000) 23751-23758
166. Toye A.A., Lippiat J.D., Proks P., Shimomura K., Bentley L., Hugill A., Mijat V., Goldsworthy M., Moir L., Haynes A., et al. A genetic and physiological study of impaired glucose homeostasis control in C57BL/6J mice. Diabetologia 48 (2005) 675-686
167. Turkkahraman D., Bircan I., Tribble N.D., Akcurin S., Ellard S., and Gloyn A.L. Permanent neonatal diabetes mellitus caused by a novel homozygous (T168A) glucokinase (GCK) mutation: initial response to oral sulphonylurea therapy. J. Pediatr. 153 (2008) 122-126
168. Unoki H., Takahashi A., Kawaguchi T., Hara K., Horikoshi M., Andersen G., Ng D.P., Holmkvist J., Borch-Johnsen K., Jorgensen T., et al. SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat. Genet. 40 (2008) 1098-1102
169. Villareal D.T., Koster J.C., Robertson H., Akrouh A., Miyake K., Bell G.I., Patterson B.W., Nichols C.G., and Polonsky K.S. Kir6.2 variant E23K increases ATP-sensitive K+ channel activity and is associated with impaired insulin release and enhanced insulin sensitivity in adults with normal glucose tolerance. Diabetes 58 (2009) 1869-1878
170. Wallace D.C. Mouse models for mitochondrial disease. Am. J. Med. Genet. 106 (2001) 71-93
171. Wambach J.A., Marshall B.A., Koster J.C., White N.H., and Nichols C.G. Successful sulfonylurea treatment of an insulin-naive neonate with diabetes mellitus due to a KCNJ11 mutation. Pediatr. Diabetes (2009) 10.1111/j.1399-5448.2009.00557.x in press. Published online July 29 2009.
172. Yang S.N., Larsson O., Branstrom R., Bertorello A.M., Leibiger B., Leibiger I.B., Moede T., Kohler M., Meister B., and Berggren P.O. Syntaxin 1 interacts with the L(D) subtype of voltage-gated Ca(2+) channels in pancreatic beta cells. Proc. Natl. Acad. Sci. USA 96 (1999) 10164-10169
173. Yang S.N., and Berggren P.O. Beta-cell CaV channel regulation in physiology and pathophysiology. Am. J. Physiol. Endocrinol. Metab. 288 (2005) E16-E28
174. Yang S.N., and Berggren P.O. CaV2.3 channel and PKClambda: new players in insulin secretion. J. Clin. Invest. 115 (2005) 16-20
175. Yasuda K., Miyake K., Horikawa Y., Hara K., Osawa H., Furuta H., Hirota Y., Mori H., Jonsson A., Sato Y., et al. Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat. Genet. 40 (2008) 1092-1097
176. Zeggini E., Weedon M.N., Lindgren C.M., Frayling T.M., Elliott K.S., Lango H., Timpson N.J., Perry J.R., Rayner N.W., Freathy R.M., et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316 (2007) 1336-1341
177. Zehetner J., Danzer C., Collins S., Eckhardt K., Gerber P.A., Ballschmieter P., Galvanovskis J., Shimomura K., Ashcroft F.M., Thorens B., et al. PVHL is a regulator of glucose metabolism and insulin secretion in pancreatic beta cells. Genes Dev. 22 (2008) 3135-3146
178. Zhang C.Y., Baffy G., Perret P., Krauss S., Peroni O., Grujic D., Hagen T., Vidal-Puig A.J., Boss O., Kim Y.B., et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 105 (2001) 745-755
179. Zhang H., Fujitani Y., Wright C.V., and Gannon M. Efficient recombination in pancreatic islets by a tamoxifen-inducible Cre-recombinase. Genesis 42 (2005) 210-217
180. Zhao Z., Zhao C., Zhang X.H., Zheng F., Cai W., Vlassara H., and Ma Z.A. Advanced glycation end products inhibit glucose-stimulated insulin secretion through nitric oxide-dependent inhibition of cytochrome c oxidase and adenosine triphosphate synthesis. Endocrinology 150 (2009) 2569-2576