Mitochondrial signals drive insulin secretion in the pancreatic β-cell

Molecular and Cellular Endocrinology

Volumn 353, Issue 1-2, 2012, Pages 128-137

  Wiederkehr, Andreas ^a   Wollheim, Claes B ^b  

^a NESTLÉ RESEARCH CENTER   (Switzerland)

^b UNIVERSITY OF GENEVA   (Switzerland)

Author keywords

Cell; Calcium; Islet; Metabolism secretion coupling; Mitochondrial matrix pH; S100G

Indexed keywords

2 OXOGLUTARIC ACID; ADENOSINE TRIPHOSPHATE; CALCIUM ION; GLUTAMIC ACID; GLUTAMINE; GUANOSINE TRIPHOSPHATE; INSULIN; MITOCHONDRIAL PROTEIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE;

ALKALINIZATION; CALCIUM TRANSPORT; CELL FUNCTION; CELL MEMBRANE DEPOLARIZATION; CELL PH; ENERGY METABOLISM; ENZYME SYNTHESIS; EXOCYTOSIS; HUMAN; INSULIN RELEASE; METABOLIC REGULATION; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL RESPIRATION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION;

ADENOSINE TRIPHOSPHATE; ANIMALS; CALCIUM; CELL MEMBRANE; DIABETES MELLITUS, TYPE 2; EXOCYTOSIS; HUMANS; INSULIN; INSULIN-SECRETING CELLS; MEMBRANE POTENTIALS; MITOCHONDRIA; OXIDATIVE PHOSPHORYLATION;

EID: 84857785686     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2011.07.016     Document Type: Review

References (106)

1. 2+-dependent mechanism. Diabetes 2002, 51(Suppl. 1):S162-S170.
2. Akhmedov D., Braun M., Mataki C., Park K.S., Pozzan T., Schoonjans K., Rorsman P., Wollheim C.B., Wiederkehr A. Mitochondrial matrix pH controls oxidative phosphorylation and metabolism-secretion coupling in INS-1E clonal beta cells. FASEB J. 2010, 24:4613-4626.
3. Baughman J.M., Perocchi F., Girgis H.S., Plovanich M., Belcher-Timme C.A., Sancak Y., Bao X.R., Strittmatter L., Goldberger O., Bogorad R.L., Koteliansky V., Mootha V.K. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 2011, 10.1038/nature10234.
4. Biddinger S.B., Kahn C.R. From mice to men: insights into the insulin resistance syndromes. Annu. Rev. Physiol. 2006, 68:123-158.
5. Blackard W.G., Nelson N.C. Portal and peripheral vein immunoreactive insulin concentrations before and after glucose infusion. Diabetes 1970, 19:302-306.
6. Blackard W.G., Nelson N.C. Portal vein insulin concentrations in diabetic subjects. Diabetes 1971, 20:286-288.
7. Brown L.J., Longacre M.J., Hasan N.M., Kendrick M.A., Stoker S.W., Macdonald M.J. Chronic reduction of the cytosolic or mitochondrial NAD(P)-malic enzyme does not affect insulin secretion in a rat insulinoma cell line. J. Biol. Chem. 2009, 284:35359-35367.
8. Carobbio S., Frigerio F., Rubi B., Vetterli L., Bloksgaard M., Gjinovci A., Pournourmohammadi S., Herrera P.L., Reith W., Mandrup S., Maechler P. Deletion of glutamate dehydrogenase in beta-cells abolishes part of the insulin secretory response not required for glucose homeostasis. J. Biol. Chem. 2009, 284:921-929.
9. 2+, substrate and ADP. Biochem. J. 1996, 318(Pt. 2):615-621.
10. 13C NMR isotopomer analysis of anaplerotic pathways in INS-1 cells. J. Biol. Chem. 2004, 279:44370-44375.
11. Clocquet A.R., Egan J.M., Stoffers D.A., Muller D.C., Wideman L., Chin G.A., Clarke W.L., Hanks J.B., Habener J.F., Elahi D. Impaired insulin secretion and increased insulin sensitivity in familial maturity-onset diabetes of the young 4 (insulin promoter factor 1 gene). Diabetes 2000, 49:1856-1864.
12. Defronzo R.A. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009, 58:773-795.
13. Denton R.M. Regulation of mitochondrial dehydrogenases by calcium ions. Biochim. Biophys. Acta 2009, 1787:1309-1316.
14. De Stefani D., Raffaello A., Teardo E., Szabo I., Rizzuto R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 2011, 10.1038/nature10230.
15. Detimary P., Van den Berghe G., Henquin J.C. Concentration dependence and time course of the effects of glucose on adenine and guanine nucleotides in mouse pancreatic islets. J. Biol. Chem. 1996, 271:20559-20565.
16. Doliba N.M., Wehrli S.L., Vatamaniuk M.Z., Qin W., Buettger C.W., Collins H.W., Matschinsky F.M. Metabolic and ionic coupling factors in amino acid-stimulated insulin release in pancreatic beta-HC9 cells. Am. J. Physiol. 2007, 292:E1507-E1519.
17. Duchen M.R., Smith P.A., Ashcroft F.M. Substrate-dependent changes in mitochondrial function, intracellular free calcium concentration and membrane channels in pancreatic beta-cells. Biochem. J. 1993, 294(Pt. 1):35-42.
18. Eliasson L., Abdulkader F., Braun M., Galvanovskis J., Hoppa M.B., Rorsman P. Novel aspects of the molecular mechanisms controlling insulin secretion. J. Physiol. 2008, 586:3313-3324.
19. Emerson P., Van Haeften T.W., Pimenta W., Plummer E., Woerle H.J., Mitrakou A., Szoke E., Gerich J., Meyer C. Different pathophysiology of impaired glucose tolerance in first-degree relatives of individuals with type 2 diabetes mellitus. Metab.: Clin. Exp. 2009, 58:602-607.
20. Farfari S., Schulz V., Corkey B., Prentki M. Glucose-regulated anaplerosis and cataplerosis in pancreatic beta-cells: possible implication of a pyruvate/citrate shuttle in insulin secretion. Diabetes 2000, 49:718-726.
21. Feldmann N., Del Rio R.M., Gjinovci A., Tamarit-Rodriguez J., Wollheim C.B., Wiederkehr A. Reduction of plasma membrane glutamate transport potentiates insulin but not glucagon secretion in pancreatic islet cells. Mol. Cell. Endocrinol. 2011, 338:46-57.
22. Fransson U., Rosengren A.H., Schuit F.C., Renstrom E., Mulder H. Anaplerosis via pyruvate carboxylase is required for the fuel-induced rise in the ATP:ADP ratio in rat pancreatic islets. Diabetologia 2006, 49:1578-1586.
23. Gauthier B.R., Wiederkehr A., Baquie M., Dai C., Powers A.C., Kerr-Conte J., Pattou F., MacDonald R.J., Ferrer J., Wollheim C.B. PDX1 deficiency causes mitochondrial dysfunction and defective insulin secretion through TFAM suppression. Cell Metab. 2009, 10:110-118.
24. Gauthier B.R., Wollheim C.B. Synaptotagmins bind calcium to release insulin. Am. J. Physiol. 2008, 295:E1279-E1286.
25. + channels in mouse B cells. J. Clin. Invest. 1992, 89:1288-1295.
26. 2+ concentration in an electrically excitable cell, the insulin-secreting pancreatic B-cell. J. Biol. Chem. 1992, 267:20713-20720.
27. Gilon P., Henquin J.C. Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function. Endocr. Rev. 2001, 22:565-604.
28. Haigis M.C., Mostoslavsky R., Haigis K.M., Fahie K., Christodoulou D.C., Murphy A.J., Valenzuela D.M., Yancopoulos G.D., Karow M., Blander G., Wolberger C., Prolla T.A., Weindruch R., Alt F.W., Guarente L. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 2006, 126:941-954.
29. Hellman B., Idahl L.A., Lernmark A., Sehlin J., Taljedal I.B. The pancreatic beta-cell recognition of insulin secretagogues. Effects of calcium and sodium on glucose metabolism and insulin release. Biochem. J. 1974, 138:33-45.
30. Henquin J.C. Regulation of insulin secretion: a matter of phase control and amplitude modulation. Diabetologia 2009, 52:739-751.
31. Hoppa M.B., Collins S., Ramracheya R., Hodson L., Amisten S., Zhang Q., Johnson P., Ashcroft F.M., Rorsman P. Chronic palmitate exposure inhibits insulin secretion by dissociation of Ca(2+) channels from secretory granules. Cell Metab. 2009, 10:455-465.
32. Hoy M., Maechler P., Efanov A.M., Wollheim C.B., Berggren P.O., Gromada J. Increase in cellular glutamate levels stimulates exocytosis in pancreatic beta-cells. FEBS Lett. 2002, 531:199-203.
33. 2 consumption in rat pancreatic islets. Diabetologia 1980, 18:395-405.
34. Ishihara H., Maechler P., Gjinovci A., Herrera P.L., Wollheim C.B. Islet beta-cell secretion determines glucagon release from neighbouring alpha-cells. Nat. Cell Biol. 2003, 5:330-335.
35. Ishihara H., Wang H., Drewes L.R., Wollheim C.B. Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate and lactate in beta cells. J. Clin. Invest. 1999, 104:1621-1629.
36. Ivarsson R., Quintens R., Dejonghe S., Tsukamoto K., in 't Veld P., Renstrom E., Schuit F.C. Redox control of exocytosis: regulatory role of NADPH, thioredoxin, and glutaredoxin. Diabetes 2005, 54:2132-2142.
37. Jensen M.V., Joseph J.W., Ronnebaum S.M., Burgess S.C., Sherry A.D., Newgard C.B. Metabolic cycling in control of glucose-stimulated insulin secretion. Am. J. Physiol. 2008, 295:E1287-E1297.
38. Jermendy A., Toschi E., Aye T., Koh A., Aguayo-Mazzucato C., Sharma A., Weir G.C., Sgroi D., Bonner-Weir S. Rat neonatal beta cells lack the specialised metabolic phenotype of mature beta cells. Diabetologia 2011, 54:594-604.
39. Jitrapakdee S., Wutthisathapornchai A., Wallace J.C., MacDonald M.J. Regulation of insulin secretion: role of mitochondrial signalling. Diabetologia 2010, 53:1019-1032.
40. Kennedy E.D., Maechler P., Wollheim C.B. Effects of depletion of mitochondrial DNA in metabolism secretion coupling in INS-1 cells. Diabetes 1998, 47:374-380.
41. 2+ in aequorin-expressing INS-1 cells. J. Clin. Invest. 1996, 98:2524-2538.
42. Kibbey R.G., Pongratz R.L., Romanelli A.J., Wollheim C.B., Cline G.W., Shulman G.I. Mitochondrial GTP regulates glucose-stimulated insulin secretion. Cell Metab. 2007, 5:253-264.
43. Klingenberg M., Rottenberg H. Relation between the gradient of the ATP/ADP ratio and the membrane potential across the mitochondrial membrane. Eur. J. Biochem./FEBS 1977, 73:125-130.
44. Kobayashi T., Nakanishi K., Nakase H., Kajio H., Okubo M., Murase T., Kosaka K. In situ characterization of islets in diabetes with a mitochondrial DNA mutation at nucleotide position 3243. Diabetes 1997, 46:1567-1571.
45. Koeck T., Olsson A.H., Nitert M.D., Sharoyko V.V., Ladenvall C., Kotova O., Reiling E., Ronn T., Parikh H., Taneera J., Eriksson J.G., Metodiev M.D., Larsson N.G., Balhuizen A., Luthman H., Stancakova A., Kuusisto J., Laakso M., Poulsen P., Vaag A., Groop L., Lyssenko V., Mulder H., Ling C. A common variant in TFB1M is associated with reduced insulin secretion and increased future risk of type 2 diabetes. Cell Metab. 2011, 13:80-91.
46. Latour M.G., Alquier T., Oseid E., Tremblay C., Jetton T.L., Luo J., Lin D.C., Poitout V. GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo. Diabetes 2007, 56:1087-1094.
47. 2+ exchanger increases mitochondrial metabolism and potentiates glucose-stimulated insulin secretion in rat pancreatic islets. Diabetes 2003, 52:965-973.
48. Li C., Buettger C., Kwagh J., Matter A., Daikhin Y., Nissim I.B., Collins H.W., Yudkoff M., Stanley C.A., Matschinsky F.M. A signaling role of glutamine in insulin secretion. J. Biol. Chem. 2004, 279:13393-13401.
49. Li C., Matter A., Kelly A., Petty T.J., Najafi H., MacMullen C., Daikhin Y., Nissim I., Lazarow A., Kwagh J., Collins H.W., Hsu B.Y., Nissim I., Yudkoff M., Matschinsky F.M., Stanley C.A. Effects of a GTP-insensitive mutation of glutamate dehydrogenase on insulin secretion in transgenic mice. J. Biol. Chem. 2006, 281:15064-15072.
50. Li C., Najafi H., Daikhin Y., Nissim I.B., Collins H.W., Yudkoff M., Matschinsky F.M., Stanley C.A. Regulation of leucine-stimulated insulin secretion and glutamine metabolism in isolated rat islets. J. Biol. Chem. 2003, 278:2853-2858.
51. 13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS). Proc. Natl. Acad. Sci. USA 2002, 99:2708-2713.
52. 2+ controls slow NAD(P)H oscillations in glucose-stimulated mouse pancreatic islets. J. Physiol. 2006, 572:379-392.
53. MacDonald M.J. The export of metabolites from mitochondria and anaplerosis in insulin secretion. Biochim. Biophys. Acta 2003, 1619:77-88.
54. MacDonald M.J., Longacre M.J., Langberg E.C., Tibell A., Kendrick M.A., Fukao T., Ostenson C.G. Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes. Diabetologia 2009, 52:1087-1091.
55. Maechler P., Kennedy E.D., Pozzan T., Wollheim C.B. Mitochondrial activation directly triggers the exocytosis of insulin in permeabilized pancreatic beta-cells. EMBO J. 1997, 16:3833-3841.
56. 2+ and insulin secretion responses in the beta cell. J. Biol. Chem. 1998, 273:20770-20778.
57. Maechler P., Wang H., Wollheim C.B. Continuous monitoring of ATP levels in living insulin secreting cells expressing cytosolic firefly luciferase. FEBS Lett. 1998, 422:328-332.
58. Maechler P., Wollheim C.B. Mitochondrial glutamate acts as a messenger in glucose-induced insulin exocytosis. Nature 1999, 402:685-689.
59. Malmgren S., Nicholls D.G., Taneera J., Bacos K., Koeck T., Tamaddon A., Wibom R., Groop L., Ling C., Mulder H., Sharoyko V.V. Tight coupling between glucose and mitochondrial metabolism in clonal beta-cells is required for robust insulin secretion. J. Biol. Chem. 2009, 284:32395-32404.
60. 2+ signal transduction in mitochondria from INS-1 clonal {beta}-cells. J. Biol. Chem. 2009, 284:515-524.
61. Matschinsky F.M. Banting Lecture 1995. A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabetes 1996, 45:223-241.
62. Murphy R., Turnbull D.M., Walker M., Hattersley A.T. Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation. Diabet. Med. 2008, 25:383-399.
63. Nicholls D.G. Simultaneous monitoring of ionophore- and inhibitor-mediated plasma and mitochondrial membrane potential changes in cultured neurons. J. Biol. Chem. 2006, 281:14864-14874.
64. Nishi Y., Fujimoto S., Sasaki M., Mukai E., Sato H., Sato Y., Tahara Y., Nakamura Y., Inagaki N. Role of mitochondrial phosphate carrier in metabolism-secretion coupling in rat insulinoma cell line INS-1. Biochem. J. 2011, 435:421-430.
65. Nolan C.J., Madiraju M.S., Delghingaro-Augusto V., Peyot M.L., Prentki M. Fatty acid signaling in the beta-cell and insulin secretion. Diabetes 2006, 55(Suppl. 2):S16-S23.
66. Ohta M., Nelson D., Nelson J., Meglasson M.D., Erecinska M. Oxygen and temperature dependence of stimulated insulin secretion in isolated rat islets of Langerhans. J. Biol. Chem. 1990, 265:17525-17532.
67. Otonkoski T., Kaminen N., Ustinov J., Lapatto R., Meissner T., Mayatepek E., Kere J., Sipila I. Physical exercise-induced hyperinsulinemic hypoglycemia is an autosomal-dominant trait characterized by abnormal pyruvate-induced insulin release. Diabetes 2003, 52:199-204.
68. 2+ exchange. Proc. Natl. Acad. Sci. USA 2010, 107:436-441.
69. Park K.S., Quan X., Das R., Xu S., Wiederkehr A., Wollheim C.B. Role of cytosolic phosphate concentration in mitochondrial function of insulin-secreting cells. Diabetologia 2010, 53(Suppl. 1):S202.
70. Patterson G.H., Knobel S.M., Arkhammar P., Thastrup O., Piston D.W. Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet beta cells. Proc. Natl. Acad. Sci. USA 2000, 97:5203-5207.
71. Perocchi F., Gohil V.M., Girgis H.S., Bao X.R., McCombs J.E., Palmer A.E., Mootha V.K. MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake. Nature 2010, 467:291-296.
72. Peyot M.L., Gray J.P., Lamontagne J., Smith P.J., Holz G.G., Madiraju S.R., Prentki M., Heart E. Glucagon-like peptide-1 induced signaling and insulin secretion do not drive fuel and energy metabolism in primary rodent pancreatic beta-cells. PLoS ONE 2009, 4:e6221.
73. Poburko D., Santo-Domingo J., Demaurex N. Dynamic regulation of the mitochondrial proton gradient during cytosolic calcium elevations. J. Biol. Chem. 2011, 286:11672-11684.
74. Pongratz R.L., Kibbey R.G., Shulman G.I., Cline G.W. Cytosolic and mitochondrial malic enzyme isoforms differentially control insulin secretion. J. Biol. Chem. 2007, 282:200-207.
75. 2+ and secretion. EMBO J. 1990, 9:53-60.
76. Pralong W.F., Hunyady L., Varnai P., Wollheim C.B., Spat A. Pyridine nucleotide redox state parallels production of aldosterone in potassium-stimulated adrenal glomerulosa cells. Proc. Natl. Acad. Sci. USA 1992, 89:132-136.
77. 2+ transients. J. Biol. Chem. 1994, 269:27310-27314.
78. Pullen T.J., Khan A.M., Barton G., Butcher S.A., Sun G., Rutter G.A. Identification of genes selectively disallowed in the pancreatic islet. Islets 2010, 2:89-95.
79. Rabaglia M.E., Gray-Keller M.P., Frey B.L., Shortreed M.R., Smith L.M., Attie A.D. Alpha-ketoisocaproate-induced hypersecretion of insulin by islets from diabetes-susceptible mice. Am. J. Physiol. 2005, 289:E218-E224.
80. Ricchelli F., Sileikyte J., Bernardi P. Shedding light on the mitochondrial permeability transition. Biochim. Biophys. Acta 2011, 1807:482-490.
81. Ronnebaum S.M., Ilkayeva O., Burgess S.C., Joseph J.W., Lu D., Stevens R.D., Becker T.C., Sherry A.D., Newgard C.B., Jensen M.V. A pyruvate cycling pathway involving cytosolic NADP-dependent isocitrate dehydrogenase regulates glucose-stimulated insulin secretion. J. Biol. Chem. 2006, 281:30593-30602.
82. Ronnebaum S.M., Jensen M.V., Hohmeier H.E., Burgess S.C., Zhou Y.P., Qian S., MacNeil D., Howard A., Thornberry N., Ilkayeva O., Lu D., Sherry A.D., Newgard C.B. Silencing of cytosolic or mitochondrial isoforms of malic enzyme has no effect on glucose-stimulated insulin secretion from rodent islets. J. Biol. Chem. 2008, 283:28909-28917.
83. Rubi B., del Arco A., Bartley C., Satrustegui J., Maechler P. The malate-aspartate NADH shuttle member aralar1 determines glucose metabolic fate, mitochondrial activity, and insulin secretion in beta cells. J. Biol. Chem. 2004, 279:55659-55666.
84. Schuit F., De Vos A., Farfari S., Moens K., Pipeleers D., Brun T., Prentki M. Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in beta cells. J. Biol. Chem. 1997, 272:18572-18579.
85. Schuit F.C., In't Veld P.A., Pipeleers D.G. Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of pancreatic beta cells. Proc. Natl. Acad. Sci. USA 1988, 85:3865-3869.
86. Sekine N., Cirulli V., Regazzi R., Brown L.J., Gine E., Tamarit-Rodriguez J., Girotti M., Marie S., MacDonald M.J., Wollheim C.B., et al. Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic beta-cells. Potential role in nutrient sensing. J. Biol. Chem. 1994, 269:4895-4902.
87. Sener A., Conget I., Rasschaert J., Leclercq-Meyer V., Villanueva-Penacarrillo M.L., Valverde I., Malaisse W.J. Insulinotropic action of glutamic acid dimethyl ester. Am. J. Physiol. 1994, 267:E573-E584.
88. Sener A., Malaisse W.J. l-Leucine and a nonmetabolized analogue activate pancreatic islet glutamate dehydrogenase. Nature 1980, 288:187-189.
89. Sener A., Malaisse W.J. Stimulation by d-glucose of mitochondrial oxidative events in islet cells. Biochem. J. 1987, 246:89-95.
90. Silva J.P., Kohler M., Graff C., Oldfors A., Magnuson M.A., Berggren P.O., Larsson N.G. Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes. Nat. Genet. 2000, 26:336-340.
91. Soejima A., Inoue K., Takai D., Kaneko M., Ishihara H., Oka Y., Hayashi J.I. Mitochondrial DNA is required for regulation of glucose-stimulated insulin secretion in a mouse pancreatic beta cell line, MIN6. J. Biol. Chem. 1996, 271:26194-26199.
92. Spegel P., Malmgren S., Sharoyko V.V., Newsholme P., Koeck T., Mulder H. Metabolomic analyses reveal profound differences in glycolytic and tricarboxylic acid cycle metabolism in glucose-responsive and -unresponsive clonal beta-cell lines. Biochem. J. 2011, 435:277-284.
93. Srinivasan M., Choi C.S., Ghoshal P., Pliss L., Pandya J.D., Hill D., Cline G., Patel M.S. β-Cell-specific pyruvate dehydrogenase deficiency impairs glucose-stimulated insulin secretion. Am. J. Physiol. 2010, 299:E910-E917.
94. Stark R., Pasquel F., Turcu A., Pongratz R.L., Roden M., Cline G.W., Shulman G.I., Kibbey R.G. Phosphoenolpyruvate cycling via mitochondrial phosphoenolpyruvate carboxykinase links anaplerosis and mitochondrial GTP with insulin secretion. J. Biol. Chem. 2009, 284:26578-26590.
95. Territo P.R., Mootha V.K., French S.A., Balaban R.S. Ca(2+) activation of heart mitochondrial oxidative phosphorylation: role of the F(0)/F(1)-ATPase. Am. J. Physiol. Cell Physiol. 2000, 278:C423-C435.
96. Thorrez L., Laudadio I., Van Deun K., Quintens R., Hendrickx N., Granvik M., Lemaire K., Schraenen A., Van Lommel L., Lehnert S., Aguayo-Mazzucato C., Cheng-Xue R., Gilon P., Van Mechelen I., Bonner-Weir S., Lemaigre F., Schuit F. Tissue-specific disallowance of housekeeping genes: the other face of cell differentiation. Genome Res. 2011, 21:95-105.
97. Verspohl E.J., Handel M., Ammon H.P. Pentosephosphate shunt activity of rat pancreatic islets: its dependence on glucose concentration. Endocrinology 1979, 105:1269-1274.
98. Weaver C.D., Gundersen V., Verdoorn T.A. A high affinity glutamate/aspartate transport system in pancreatic islets of Langerhans modulates glucose-stimulated insulin secretion. J. Biol. Chem. 1998, 273:1647-1653.
99. Weir G.C., Bonner-Weir S. Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes 2004, 53(Suppl. 3):S16-S21.
100. Wiederkehr A., Park K.S., Dupont O., Demaurex N., Pozzan T., Cline G.W., Wollheim C.B. Matrix alkalinization: a novel mitochondrial signal for sustained pancreatic beta-cell activation. EMBO J. 2009, 28:417-428.
101. Wiederkehr A., Szanda G., Akhmedov D., Mataki C., Heizmann C.W., Schoonjans K., Pozzan T., Spat A., Wollheim C.B. Mitochondrial matrix calcium is an activating signal for hormone secretion. Cell Metab. 2011, 13:601-611.
102. Wollheim C.B. Beta-cell mitochondria in the regulation of insulin secretion: a new culprit in type II diabetes. Diabetologia 2000, 43:265-277.
103. Wollheim C.B., Sharp G.W. Regulation of insulin release by calcium. Physiol. Rev. 1981, 61:914-973.
104. Xu J., Han J., Long Y.S., Epstein P.N., Liu Y.Q. The role of pyruvate carboxylase in insulin secretion and proliferation in rat pancreatic beta cells. Diabetologia 2008, 51:2022-2030.
105. Xu J., Han J., Long Y.S., Lock J., Weir G.C., Epstein P.N., Liu Y.Q. Malic enzyme is present in mouse islets and modulates insulin secretion. Diabetologia 2008, 51:2281-2289.
106. Zhou Y., Jetton T.L., Goshorn S., Lynch C.J., She P. Transamination is required for {alpha}-ketoisocaproate but not leucine to stimulate insulin secretion. J. Biol. Chem. 2010, 285:33718-33726.