Novel regulation of insulin secretion: The role of mitochondria

Current Opinion in Investigational Drugs

Volumn 4, Issue 10, 2003, Pages 1166-1172

  Maechler, Pierre ^a  

^a UNIVERSITY OF GENEVA MEDICAL SCHOOL   (Switzerland)

Author keywords

Cell; Calcium; Glutamate dehydrogenase; Insulin secretion; Mitochondria; Pancreatic islet

Indexed keywords

ADENOSINE TRIPHOSPHATE; ANTIOXIDANT; CALCIUM CHANNEL BLOCKING AGENT; CALCIUM ION; GLUCOSE; INSULIN; NUCLEOTIDE; PYRUVIC ACID; SULFONYLUREA;

CELL DAMAGE; CELL MEMBRANE POTENTIAL; CELL METABOLISM; CELL ORGANELLE; COUPLING FACTOR; CYTOSOL; DRUG MECHANISM; EXOCYTOSIS; HUMAN; INSULIN RELEASE; METABOLITE; MITOCHONDRION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NUCLEOTIDE SEQUENCE; PANCREAS ISLET BETA CELL; RESPIRATORY CHAIN; REVIEW;

ADENOSINE TRIPHOSPHATE; ANIMALS; CALCIUM; DIABETES MELLITUS; DNA, MITOCHONDRIAL; ELECTRON TRANSPORT; EXOCYTOSIS; GLUCOSE; HUMANS; INSULIN; MEMBRANE PROTEINS; MITOCHONDRIA; NUCLEOTIDES; POTASSIUM CHANNELS; PROTONS; PYRUVIC ACID;

EID: 0242658614     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (84)

1. Matschinsky FM: Banting Lecture 1995. A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabetes (1996) 45(2):223-241.
2. Grimsby J, Sarabu R, Corbett WL, Haynes NE, Bizzarro FT, Coffey JW, Guertin KR, Hilliard DW, Kester RF, Mahaney PE, Maraus L et al: Allosteric activators of glucokinase: Potential role in diabetes therapy. Science (2003) 301(5631):370-373.
3. 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 β cells. J Biol Chem (1997) 272(30):18572-18579. A detailed study on the fate of glucose in β-cells and the associated remarkable importance of anaplerosis.
4. MacDonald MJ: High content of mitochondrial glycerol-3-phosphate dehydrogenase in pancreatic islets and its inhibition by diazoxide. J Biol Chem (1981) 256(16):8287-8290.
5. Eto K, Tsubamoto Y, Terauchi Y, Sugiyama T, Kishimoto T, Takahashi N, Yamauchi N, Kubota N, Murayama S, Aizawa T, Akanuma Y et al: Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion. Science (1999) 283(5404):981-985. Demonstration of the importance of mitochondrial proton shuttles in β-cells by the combined use of a transgenic mouse model together with inhibitors.
6. MacDonald MJ: Feasibility of a mitochondrial pyruvate malate shuttle in pancreatic islets. Further implication of cytosolic NADPH in insulin secretion. J Biol Chem (1995) 270(34):20051-20058.
7. Farfari S, Schulz V, Corkey B, Prentki M: Glucose-regulated anaplerosis and cataplerosis in pancreatic β-cells: Possible implication of a pyruvate/citrate shuttle in insulin secretion. Diabetes (2000) 49(5):718-726.
8. Sekine N, Cirulli V, Regazzi R, Brown LJ, Gine E, Tamarit-Rodriguez J, Girotti M, Marie S, MacDonald MJ, Wollheim CB: Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic β-cells. Potential role in nutrient sensing. J Biol Chem (1994) 269(7):4895-4902.
9. Newgard CB, McGarry JD: Metabolic coupling factors in pancreatic β-cell signal transduction. Annu Rev Biochem (1995) 64:689-719.
10. Brennan L, Shine A, Hewage C, Malthouse JP, Brindle KM, McClenaghan N, Flatt PR, Newsholme P: A nuclear magnetic resonance-based demonstration of substantial oxidative L-alanine metabolism and L-alanine-enhanced glucose metabolism in a clonal pancreatic β-cell line: Metabolism of L-alanine is important to the regulation of insulin secretion. Diabetes (2002) 51(6):1714-1721.
11. 13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS). Proc Natl Acad Sci USA (2002) 99(5):2708-2713.
12. Maechler P, Wollheim CB: Mitochondrial glutamate acts as a messenger in glucose-induced insulin exocytosis. Nature (1999) 402(6762):685-689. Participation of glutamate as a mitochondria-derived intracellular messenger in glucose-stimulated insulin secretion is described.
13. Owen OE, Kalhan SC, Hanson RW: The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem (2002) 277(34):30409-30412. A concise and clear review describing the pathways 'in and out the TCA cycle', ie, anaplerosis and cataplerosis, respectively.
14. Nissim I: Newer aspects of glutamine/glutamate metabolism: The role of acute pH changes. Am J Physiol (1999) 277(4 Pt 2):F493-F497.
15. Broca C, Brennan L, Petit P, Newsholme P, Maechler P: Mitochondria-derived glutamate at the interplay between branched-chain amino acid and glucose-induced insulin secretion. FEBS Lett (2003) 545(2-3):167-172.
16. McCormack JG, Halestrap AP, Denton RM: Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev (1990) 70(2):391-425.
17. Duchen MR: Contributions of mitochondria to animal physiology: From homeostatic sensor to calcium signalling and cell death. J Physiol (1999) 516(1):1-17. An extensive review on the role of calcium in mitochondria.
18. Wallace DC: Mitochondrial diseases in man and mouse. Science (1999) 283(5407):1482-1488. A classic and essential review on basic mitochondria and mitochondrial diseases.
19. Antinozzi PA, Ishihara H, Newgard CB, Wollheim CB: Mitochondrial metabolism sets the maximal limit of fuel-stimulated insulin secretion in a model pancreatic β cell: A survey of four fuel secretagogues. J Biol Chem (2002) 277(14):11746-11755.
20. 2+ in aequorin-expressing INS-1 cells. J Clin Invest (1996) 98(11):2524-2538.
21. 2+ with recombinant targeted aequorin: Significance for the regulation of pyruvate dehydrogenase activity. Proc Natl Acad Sci USA (1996) 93(11):5489-5494.
22. 2+ transients. J Biol Chem (1994) 269(44):27310-27314.
23. Kennedy HJ, Pouli AE, Ainscow EK, Jouaville LS, Rizzuto R, Rutter GA: Glucose generates sub-plasma membrane ATP microdomains in single islet β-cells. Potential role for strategically located mitochondria. J Biol Chem (1999) 274(19):13281-13291.
24. Wollheim CB, Maechler P: β-Cell mitochondria and insulin secretion: Messenger role of nucleotides and metabolites. Diabetes (2002) 51(Suppl 1):S37-S42.
25. Rizzuto R, Bernardi P, Pozzan T: Mitochondria as all-round players of the calcium game. J Physiol (2000) 529(Pt 1):37-47.
26. 2+ exchanger increases mitochondrial metabolism and potentiates glucose-stimulated insulin secretion in rat pancreatic islets. Diabetes (2003) 52(4):965-973. Demonstration that a drug can selectively improve mitochondrial metabolism and thereby potentiate glucose-stimulated insulin secretion.
27. Ashcroft FM, Harrison DE, Ashcroft SJ: Glucose induces closure of single potassium channels in isolated rat pancreatic β-cells. Nature (1984) 312(5993):446-448.
28. + channel in insulin-secreting pancreatic β-cells. J Mol Endocrinol (1999) 22(2):113-123.
29. Rorsman P: The pancreatic β-cell as a fuel sensor: An electrophysiologist's viewpoint. Diabetologia (1997) 40(5):487-495.
30. Ligon B, Boyd AE III, Dunlap K: Class A calcium channel variants in pancreatic islets and their role in insulin secretion. J Biol Chem (1998) 273(22):13905-13911.
31. Henquin JC: Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes (2000) 49(11):1751-1760. A detailed review on the so-called K-ATP-independent pathway (renamed as amplifying pathway here) a decade after its discovery by different research groups (see also references [32], [33] and [34]).
32. Panten U, Schwanstecher M, Wallasch A, Lenzen S: Glucose both inhibits and stimulates insulin secretion from isolated pancreatic islets exposed to maximally effective concentrations of sulfonylureas. Naunyn Schmiedebergs Arch Pharmacol (1988) 338(4):459-462.
33. + channels in mouse B cells. J Clin Invest (1992) 89(4):1288-1295.
34. 2+ influx in rat pancreatic B-cell. Diabetes (1992) 41(4):438-443.
35. Yu W, Niwa T, Fukasawa T, Hidaka H, Senda T, Sasaki Y, Niki I: Synergism of protein kinase A, protein kinase C, and myosin light-chain kinase in the secretory cascade of the pancreatic β-cell. Diabetes (2000) 49(6):945-952.
36. Varadi A, Ainscow EK, Allan VJ, Rutter GA: Involvement of conventional kinesin in glucose-stimulated secretory granule movements and exocytosis in clonal pancreatic β-cells. J Cell Sci (2002) 115(21):4177-4189.
37. 2+-independent insulin secretion from permeabilized RINm5F cells. J Biol Chem (1987) 262(11):5049-5056.
38. Rorsman P, Eliasson L, Renstrom E, Gromada J, Barg S, Gopel S: The cell physiology of biphasic insulin secretion. News Physiol Sci (2000) 15:72-77.
39. Detimary P, Van Den Berghe G, Henquin JC: Concentration dependence and time course of the effects of glucose on adenine and guanine nucleotides in mouse pancreatic islets. J Biol Chem (1996) 271(34):20559-20565.
40. Lang J: Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion. Eur J Biochem (1999) 259(1-2):3-17.
41. Ahren B: Autonomic regulation of islet hormone secretion - Implications for health and disease. Diabetologia (2000) 43(4):393-410.
42. Schuit FC, Huypens P, Heimberg H, Pipeleers DG: Glucose sensing in pancreatic β-cells: A model for the study of other glucose-regulated cells in gut, pancreas, and hypothalamus. Diabetes (2001) 50(1):1-11.
43. Huypens P, Ling Z, Pipeleers D, Schuit F: Glucagon receptors on human islet cells contribute to glucose competence of insulin release. Diabetologia (2000) 43(8):1012-1019.
44. Liang Y, Matschinsky FM: Content of CoA-esters in perifused rat islets stimulated by glucose and other fuels. Diabetes (1991) 40(3):327-333.
45. Prentki M, Vischer S, Glennon MC, Regazzi R, Deeney JT, Corkey BE: Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion. J Biol Chem (1992) 267(9):5802-5810. Participation of long-chain acyl-CoAs as metabolic coupling factors in metabolism-secretion coupling is described.
46. Deeney JT, Gromada J, Hoy M, Olsen HL, Rhodes CJ, Prentki M, Berggren PO, Corkey BE: Acute stimulation with long chain acyl-CoA enhances exocytosis in insulin-secreting cells (HIT T-15 and NMRI β-cells). J Biol Chem (2000) 275(13):9363-9368.
47. Antinozzi PA, Segall L, Prentki M, McGarry JD, Newgard CB: Molecular or pharmacologic perturbation of the link between glucose and lipid metabolism is without effect on glucose-stimulated insulin secretion. A re-evaluation of the long-chain acyl-CoA hypothesis. J Biol Chem (1998) 273-26:16146-16154.
48. Prentki M, Joly E, El-Assaad W, Roduit R: Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: Role in β-cell adaptation and failure in the etiology of diabetes. Diabetes (2002) 51(suppl 3):S405-S413.
49. Maechler P, Antinozzi PA, Wollheim CB: Modulation of glutamate generation in mitochondria affects hormone secretion in INS-1E β cells. IUBMB Life (2000) 50(1):27-31.
50. Maechler P, Wollheim CB: Mitochondrial signals in glucose-stimulated insulin secretion in the β cell. J Physiol (2000) 529(1):49-56.
51. Rubi B, Ishihara H, Hegardt FG, Wollheim CB, Maechler P: GAD65-mediated glutamate decarboxylation reduces glucose-stimulated insulin secretion in pancreatic β cells. J Biol Chem (2001) 276(39):36391-36396.
52. Bertrand G, Ishiyama N, Nenguin M, Ravier MA, Henquin JC: The elevation of glutamate content and the amplification of insulin secretion in glucose-stimulated pancreatic islets are not causally related. J Biol Chem (2002) 277(36):32883-32891.
53. Danielsson A, Hellman B, Idahl LA: Levels of α-ketoglutarate and glutamate in stimulated pancreatic β-cells. Horm Metab Res (1970) 2(1):28-31.
54. MacDonald MJ, Fahien LA: Glutamate is not a messenger in insulin secretion. J Biol Chem (2000) 275(44):34025-34027.
55. Maechler P, Kennedy ED, Pozzan T, Wollheim CB: Mitochondrial activation directly triggers the exocytosis of insulin in permeabilized pancreatic β-cells. EMBO J (1997) 16(13):3833-3841.
56. Hoy M, Maechler P, Efanov AM, Wollheim CB, Berggren PO, Gromada J: Increase in cellular glutamate levels stimulates exocytosis in pancreatic β-cells. FEBS Lett (2002) 531(2):199-203.
57. Bai L, Zhang X, Ghishan FK: Characterization of vesicular glutamate transporter in pancreatic α- and β-cells and its regulation by glucose. Am J Physiol Gastrointest Liver Physiol (2003) 284(5):G808-G814.
58. Eto K, Yamashita T, Hirose K, Tsubamoto Y, Ainscow EK, Rutter GA, Kimura S, Noda M, Iino M, Kodawaki T: Glucose metabolism and glutamate analog acutely alkalinize pH of insulin secretory vesicles of pancreatic β-cells. Am J Physiol Endocrinol Metab (2003) 285(2):E262-E271.
59. Hudson RC, Daniel RM: L-Glutamate dehydrogenases: Distribution, properties and mechanism. Comp Biochem Physiol B (1993) 106(4):767-792.
60. Anderson CM, Swanson RA: Astrocyte glutamate transport: Review of properties, regulation, and physiological functions. Glia (2000) 32(1):1-14.
61. Maechler P: Mitochondria as the conductor of metabolic signals for insulin exocytosis in pancreatic β-cells. Cell Mol Life Sci (200) 59(11):1803-1818.
62. Bryla J, Michalik M, Nelson J, Erecinska M: Regulation of the glutamate dehydrogenase activity in rat islets of Langerhans and its consequence on insulin release. Metabolism (1994) 43(9):1187-1195.
63. Yang SJ, Huh JW, Kim MJ, Lee WJ, Kim TU, Choi SY, Cho SW: Regulatory effects of 5′-deoxypyridoxal on glutamate dehydrogenase activity and insulin secretion in pancreatic islets. Biochimie (2003) 85(6):581-586.
64. Stanley CA, Lieu YK, Hsu BY, Burlina AB, Greenberg CR, Hopwood NJ, Perlman K, Rich BH, Zammarchi E, Poncz M: Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med (1998) 338(19):1352-1357. Demonstration that one of the hyperinsulinism syndromes is caused by activating mutations in the mitochondrial enzyme glutamate dehydrogenase with reduced sensitivity to the allosteric inhibitory action of GTP.
65. Beckman KB, Ames BN: The free radical theory of aging matures. Physiol Rev (1998) 8(2):547-581.
66. Tiedge M, Lortz S, Drinkgern J, Lenzen S: Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes (1997) 46(11):1733-1742.
67. Maechler P, JornotL, Wollheim CB: Hydrogen peroxide alters mitochondrial activation and insulin secretion in pancreatic β cells. J Biol Chem (1999) 274(39):27905-27913.
68. Bindokas VP, Kuznetsov A, Sreenan S, Polonsky KS, Roe MW, Philipson LH: Visualizing superoxide production in normal and diabetic rat islets of Langerhans. J Biol Chem (2003) 278(11):9796-9801.
69. Coordt MC, Ruhe RC, McDonald RB: Aging and insulin secretion. Proc Soc Exp Biol Med (1995) 209(3):213-222.
70. Mandrup-Poulsen T: β-Cell apoptosis: Stimuli and signaling. Diabetes (2001) 50(Suppl 1):S58-S63.
71. Fajans SS, Bell GI, Polonsky KS: Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med (2001) 345(13):971-980.
72. Byrne MM, Sturis J, Menzel S, Yamagata K, Fajans SS, Dronsfield MJ, Brain SC, Hattersley AT, Velho G, Froguel P, Bell GI et al. Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12. Diabetes (1996) 45(11):1503-1510.
73. Wang H, Maechler P, Antinozzi PA, Hagenfeldt KA, Wollheim CB: Hepatocyte nuclear factor 4α regulates the expression of pancreatic β-cell genes implicated in glucose metabolism and nutrient-induced insulin secretion. J Biol Chem (2000) 275(46):35953-35959.
74. Wang H, Antinozzi PA, Hagenfeldt KA, Maechler P, Wollheim CB: Molecular targets of a human HNF1α mutation responsible for pancreatic β-cell dysfunction. EMBO J (2000) 19(16):4257-4264.
75. Chan CB, De Leo D, Joseph JW, McQuaid TS, Ha XF, Xu F, Tsushima RG, Pennefather PS, Salapatek AM, Wheeler MB: Increased uncoupling protein-2 levels in β-cells are associated with impaired glucose-stimulated insulin secretion: Mechanism of action. Diabetes (2001) 50(6):1302-1310.
76. Zhang CY, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, Hagen T, Vidal-Puig AJ, Boss O, Kim YB, Zheng XX et al.: Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, β cell dysfunction, and type 2 diabetes. Cell (2001) 105(6):745-755.
77. Joseph JW, Koshkin V, Zhang CY, Wang J, Lowell BB, Chan CB, Wheeler MB: Uncoupling protein 2 knockout mice have enhanced insulin secretory capacity after a high-fat diet. Diabetes (2002) 51(11):3211-3219.
78. Li LX, Skorpen F, Egeberg K, Jorgensen IH, Grill V: Uncoupling protein-2 participates in cellular defense against oxidative stress in clonal β-cells. Biochem Biophys Res Commun (2001) 282(1):273-277.
79. Maassen JA, Van Essen E, Van Den Ouweland JM, Lemkes HH: Molecular and clinical aspects of mitochondrial diabetes mellitus. Exp Clin Endocrinol Diabetes (2001) 109(3):127-134.
80. Maechler P, Wollheim CB: Mitochondrial function in normal and diabetic β-cells. Nature (2001) 414(6865):807-812.
81. Silva JP, Kohler M, Graff C, Oldfors A, Magnuson MA, Berggren PO, Larsson NG: Impaired insulin secretion and β-cell loss in tissue-specific knockout mice with mitochondrial diabetes. Nat Genet (2000) 26(3):336-340. Expression of mitochondrial DNA is controlled by a nuclear-encoded transcription factor, mitochondrial transcription factor A (TFAM). Here, the authors specifically disrupted the Tfam gene in β-cells of transgenic mice, causing a diabetic phenotype. These animals represent the first model of human mitochondrial diabetes.
82. Soejima A, Inoue K, Takai D, Kaneko M, Ishihara H, Oka Y, Hayashi JI: Mitochondrial DNA is required for regulation of glucose-stimulated insulin secretion in a mouse pancreatic β cell line, MIN6. J Biol Chem (1996) 271(42):26194-26199.
83. Kennedy ED, Maechler P, Wollheim CB: Effects of depletion of mitochondrial DNA in metabolism secretion coupling in INS-1 cells. Diabetes (1998) 47(3):374-380.
84. Tsuruzoe K, Araki E, Furukawa N, Shirotani T, Matsumoto K, Kaneko K, Motoshima H, Yoshizato K, Shirakami A, Kishikawa H, Miyazaki J et al.: Creation and characterization of a mitochondrial DNA-depleted pancreatic β-cell line: Impaired insulin secretion induced by glucose, leucine, and sulfonylureas. Diabetes (1998) 47(4):621-631.