Metabolic signaling of insulin secretion by pancreatic β-cell and its derangement in type 2 diabetes

European Review for Medical and Pharmacological Sciences

Volumn 18, Issue 15, 2014, Pages 2215-2227

  Zou, C Y ^a,b,c   Gong, Y ^a,b,c   Liang, J ^a,b,c  

^a XUZHOU MEDICAL UNIVERSITY   (China)

^b SOUTHEAST UNIVERSITY   (China)

^c Xuzhou Institute of Medical Sciences Xuzhou Institute of Diabetes ^*  (China)

Author keywords

Insulin secretion; Pancreatic cell; Type 2 diabetes mellitus

Indexed keywords

ADENOSINE DIPHOSPHATE; ADENOSINE PHOSPHATE; ADENOSINE TRIPHOSPHATE; ADENYLATE KINASE; FATTY ACID; GLUCOSE; GLUTAMATE DEHYDROGENASE; GLUTAMIC ACID; GUANOSINE TRIPHOSPHATE; INSULIN; MALONYL COENZYME A; PYRUVIC ACID; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; TRIACYLGLYCEROL; AMINO ACID;

ANAPLEROSIS; CATAPLEROSIS; CITRIC ACID CYCLE; COUPLING FACTOR; GLUCOSE METABOLISM; HUMAN; INSULIN RELEASE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; LIPID METABOLISM; METABOLISM; PHYSIOLOGY;

AMINO ACIDS; ANIMALS; DIABETES MELLITUS, TYPE 2; GLUCOSE; HUMANS; INSULIN; INSULIN-SECRETING CELLS; LIPID METABOLISM; SIGNAL TRANSDUCTION;

EID: 84926083664     PISSN: 11283602     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (99)

1. Nolan Cj, Damm P, Prentki M. Type 2 Diabetes Across Generations: From Pathophysiology To Prevention And Management. Lancet 2011; 378: 169-181.
2. Ashcroft Fm, Rorsman P. Diabetes Mellitus And The Beta Cell: The Last Ten Years. Cell 2012; 148: 1160-1171.
3. Martin-Gronert Ms, Ozanne Se. Metabolic Programming Of Insulin Action And Secretion. Diabetes Obes Metab 2012; 14(Suppl 3): 29-39.
4. Newsholme P, Krause M. Nutritional Regulation Of Insulin Secretion: Implications For Diabetes. Clin Biochem Rev 2012; 33: 35-47.
5. Nolan Cj, Prentki M. The Islet Beta-Cell: Fuel Responsive And Vulnerable. Trends Endocrinol Metab 2008; 19: 285-291.
6. Meglasson Md, Matschinsky Fm. Pancreatic Islet Glucose Metabolism And Regulation Of Insulin Secretion. Diabetes Metab Rev 1986; 2: 163-214.
7. 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.
8. Ruiz De Azua I, Gautam D, Guettier Jm, Wess J. Novel Insights Into The Function Of Beta-Cell M3 Muscarinic Acetylcholine Receptors: Therapeutic Implications. Trends Endocrinol Metab 2011; 22: 74-80.
9. Matschinsky Fm. A Lesson In Metabolic Regulation Inspired By The Glucokinase Glucose Sensor Paradigm. Diabetes 1996; 45: 223-241.
10. Prentki M. New Insights Into Pancreatic Beta-Cell Metabolic Signaling In Insulin Secretion. Eur J Endocrinol 1996; 134: 272-286.
11. Peyot Ml, Gray Jp, Lamontagne J, Smith Pj, Holz Gg, Madiraju Sr, Prentki M, Heart E. Glucagonlike 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.
12. Bennett K, James C, Hussain K. Pancreatic Beta-Cell Katp Channels: Hypoglycaemia And Hyperglycaemia. Rev Endocr Metab Disord 2010; 11: 157-163.
13. Nichols Cg, Remedi Ms. The Diabetic Beta-Cell: Hyperstimulated Vs. Hyperexcited. Diabetes Obes Metab 2012; 14(Suppl 3): 129-135.
14. Porat S, Weinberg-Corem N, Tornovsky-Babaey S, Schyr-Ben-Haroush R, Hija A, Stolovich-Rain M, Dadon D, Granot Z, Ben-Hur V, White P, Girard Ca, Karni R, Kaestner Kh, Ashcroft Fm, Magnuson Ma, Saada A, Grimsby J, Glaser B, Dor Y. Control Of Pancreatic Beta Cell Regeneration By Glucose Metabolism. Cell Metab 2011; 13: 440-449.
15. Levitt He, Cyphert Tj, Pascoe Jl, Hollern Da, Abraham N, Lundell Rj, Rosa T, Romano Lc, Zou B, O'Donnell Cp, Stewart Af, Garcia-Ocaña A, Alonso Lc. Glucose Stimulates Human Beta Cell Replication In Vivo In Islets Transplanted Into Nod-Severe Combined Immunodeficiency (Scid) Mice. Diabetologia 2011; 54: 572-582.
16. Meglasson Md, Matschinsky Fm. New Perspectives On Pancreatic Islet Glucokinase. Am J Physiol 1984; 246: E1-13.
17. Prentki M, Nolan Cj. Islet Beta Cell Failure In Type 2 Diabetes. J Clin Invest 2006; 116: 1802-1812.
18. Sekine N, Cirulli V, Regazzi R, Brown Lj, Gine E, Tamarit-Rodriguez J, Girotti M, Marie S, Macdonald Mj, Wollheim Cb, Rutter Ga. 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.
19. Schuit F, Van Lommel L, Granvik M, Goyvaerts L, De Faudeur G, Schraenen A, Lemaire K. Beta-Cellspecific Gene Repression: A Mechanism To Protect Against Inappropriate Or Maladjusted Insulin Secretion? Diabetes 2012; 61: 969-975.
20. Kwan Ep, Gaisano Hy. Rescuing The Subprime Meltdown In Insulin Exocytosis In Diabetes. Ann N Y Acad Sci 2009; 1152: 154-164.
21. Kasai H, Hatakeyama H, Ohno M, Takahashi N. Exocytosis In Islet Beta-Cells. Adv Exp Med Biol 2010; 654: 305-338.
22. Suckow At, Craige B, Faundez V, Cain Wj, Chessler Sd. An Ap-3-Dependent Mechanism Drives Synaptic-Like Microvesicle Biogenesis In Pancreatic Islet Beta-Cells. Am J Physiol Endocrinol Metab 2010; 299: E23-32.
23. Curry Dl, Bennett Ll, Grodsky Gm. Dynamics Of Insulin Secretion By The Perfused Rat Pancreas. Endocrinology 1968; 83: 572-584.
24. Seino S, Shibasaki T, Minami K. Dynamics Of Insulin Secretion And The Clinical Implications For Obesity And Diabetes. J Clin Invest 2011; 121: 2118-2125.
25. Wang Z, Thurmond Dc. Mechanisms Of Biphasic Insulin-Granule Exocytosis-Roles Of The Cytoskeleton, Small Gtpases And Snare Proteins. J Cell Sci 2009; 122: 893-903.
26. Michael Dj, Xiong W, Geng X, Drain P, Chow Rh. Human Insulin Vesicle Dynamics During Pulsatile Secretion. Diabetes 2007; 56: 1277-1288.
27. Prentki M, Matschinsky Fm, Madiraju Sr. Metabolic Signaling In Fuel-Induced Insulin Secretion. Cell Metab 2013; 18: 162-185.
28. 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: 20051-20058.
29. 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: 18572-18579.
30. Srinivasan M, Choi Cs, Ghoshal P, Pliss L, Pandya Jd, Hill D, Cline G, Patel Ms. {Beta}-Cell-Specific Pyruvate Dehydrogenase Deficiency Impairs Glucose-Stimulated Insulin Secretion. Am J Physiol Endocrinol Metab 2010; 299: E910-917.
31. Cline Gw, Lepine Rl, Papas Kk, Kibbey Rg, Shulman Gi. 13C Nmr Isotopomer Analysis Of Anaplerotic Pathways In Ins-1 Cells. J Biol Chem 2004; 279: 44370-44375.
32. Farfari S, Schulz V, Corkey B, Prentki M. Glucoseregulated Anaplerosis And Cataplerosis In Pancreatic Beta-Cells: Possible Implication Of A Pyruvate/Citrate Shuttle In Insulin Secretion. Diabetes 2000; 49: 718-726.
33. Hasan Nm, Longacre Mj, Stoker Sw, Boonsaen T, Jitrapakdee S, Kendrick Ma, Wallace Jc, Macdonald Mj. Impaired Anaplerosis And Insulin Secretion In Insulinoma Cells Caused By Small Interfering Rna-Mediated Suppression Of Pyruvate Carboxylase. J Biol Chem 2008; 283: 28048-28059.
34. Xu J, Han J, Long Ys, Epstein Pn, Liu Yq. The Role Of Pyruvate Carboxylase In Insulin Secretion And Proliferation In Rat Pancreatic Beta Cells. Diabetologia 2008; 51: 2022-2030.
35. Macdonald Mj, Longacre Mj, Langberg Ec, Tibell A, Kendrick Ma, Fukao T, Ostenson Cg. Decreased Levels Of Metabolic Enzymes In Pancreatic Islets Of Patients With Type 2 Diabetes. Diabetologia 2009; 52: 1087-1091.
36. Maechler P, Li N, Casimir M, Vetterli L, Frigerio F, Brun T. Role Of Mitochondria In Beta-Cell Function And Dysfunction. Adv Exp Med Biol 2010; 654: 193-216.
37. Stanley Ca. Two Genetic Forms Of Hyperinsulinemic Hypoglycemia Caused By Dysregulation Of Glutamate Dehydrogenase. Neurochem Int 2011; 59: 465-472.
38. Sugden Mc, Holness Mj. The Pyruvate Carboxylase-Pyruvate Dehydrogenase Axis In Islet Pyruvate Metabolism: Going Round In Circles? Islets 2011; 3: 302-319.
39. Macdonald Mj, Fahien La, Brown Lj, Hasan Nm, Buss Jd, Kendrick Ma. Perspective: Emerging Evidence For Signaling Roles Of Mitochondr Ial Anaplerotic Products In Insulin Secretion. Am J Physiol Endocrinol Metab 2005; 288: E1-15.
40. Jensen Mv, Joseph Jw, Ronnebaum Sm, Burgess Sc, Sherry Ad, Newgard Cb. Metabolic Cycling In Control Of Glucose-Stimulated Insulin Secretion. Am J Physiol Endocrinol Metab 2008; 295: E1287-1297.
41. Fransson U, Rosengren Ah, Schuit Fc, Renstrom E, Mulder H. Anaplerosis Via Pyruvate Carboxylase Is Required For The Fuel-Induced R Ise In The Atp:Adp Ratio In Rat Pancreatic Islets. Diabetologia 2006; 49: 1578-1586.
42. Flamez D, Berger V, Kruhoffer M, Orntoft T, Pipeleers D, Schuit Fc. Critical Role For Cataplerosis Via Citrate In Glucose-Regulated Insulin Release. Diabetes 2002; 51: 2018-2024.
43. Corkey Be, Tornheim K, Deeney Jt, Glennon Mc, Parker Jc, Matschinsky Fm, Ruderman Nb, Prentki M. Linked Oscillations Of Free Ca2+ And The Atp/Adp Ratio In Permeabilized Rinm5F Insulinoma Cells Supplemented With A Glycolyzing Cellfree Muscle Extract. J Biol Chem 1988; 263: 4254-4258.
44. Longo Ea, Tornheim K, Deeney Jt, Varnum Ba, Tillotson D, Prentki M, Corkey Be. Oscillations In Cytosolic Free Ca2+, Oxygen Consumption, And Insulin Secretion In Glucose-Stimulated Rat Pancreatic Islets. J Biol Chem 1991; 266: 9314-9319.
45. Macdonald Mj, Fahien La, Buss Jd, Hasan Nm, Fallon Mj, Kendrick Ma. Citrate Oscillates In Liver And Pancreatic Beta Cell Mitochondria And In Ins-1 Insulinoma Cells. J Biol Chem 2003; 278: 51894-51900.
46. Ronnebaum Sm, Ilkayeva O, Burgess Sc, Joseph Jw, Lu D, Stevens Rd Becker Tc, Sherry Ad, Newgard Cb, Jensen Mv. A Pyruvate Cycling Pathway Involving Cytosolic Nadp-Dependent Isocitrate Dehydrogenase Regulates Glucose-Stimulated Insulin Secretion. J Biol Chem 2006; 281: 30593-30602.
47. Guay C, Joly E, Pepin E, Barbeau A, Hentsch L, Pineda M, Madiraju Sr, Brunengraber H, Prentki M. A Role For Cytosolic Isocitrate Dehydrogenase As A Negative Regulator Of Glucose Signaling For Insulin Secretion In Pancreatic B-Cells. Plos One 2013; 8: E77097.
48. Guay C, Madiraju Sr, Aumais A, Joly E, Prentki M. A Role For Atp-Citrate Lyase, Malic Enzyme, And Pyruvate/Citrate Cycling In Glucose-Induced Insulin Secretion. J Biol Chem 2007; 282: 35657-35665.
49. Pongratz Rl, Kibbey Rg, Shulman Gi, Cline Gw. Cytosolic And Mitochondrial Malic Enzyme Isoforms Differentially Control Insulin Secretion. J Biol Chem 2007; 282: 200-207.
50. Xu J, Han J, Long Ys, Lock J, Weir Gc, Epstein Pn, Liu Yq. Malic Enzyme Is Present In Mouse Islets And Modulates Insulin Secretion. Diabetologia 2008; 51: 2281-2289.
51. Stark R, Pasquel F, Turcu A, Pongratz Rl, Roden M, Cline Gw, Shulman Gi, Kibbey Rg. Phosphoenolpyruvate Cycling Via Mitochondrial Phosphoenolpyruvate Carboxykinase Links Anaplerosis And Mitochondrial Gtp With Insulin Secretion. J Biol Chem 2009; 284: 26578-26590.
52. Joseph Jw, Jensen Mv, Ilkayeva O, Palmieri F, Alarcon C, Rhodes Cj, Newgard Cb. The Mitochondrial Citrate/Isocitrate Carrier Plays A Regulatory Role In Glucose-Stimulated Insulin Secretion. J Biol Chem 2006; 281: 35624-35632.
53. Heart E, Cline Gw, Collis Lp, Pongratz Rl, Gray Jp, Smith Pj. Role For Malic Enzyme, Pyruvate Carboxylation, And Mitochondrial Malate Import In Glucose-Stimulated Insulin Secretion. Am J Physiol Endocrinol Metab 2009; 296: E1354-1362.
54. Joseph Jw, Odegaard Ml, Ronnebaum Sm, Burgess Sc, Muehlbauer J, Sherry Ad, Newgard Cb. Normal Flux Through Atp-Citrate Lyase Or Fatty Acid Synthase Is Not Required For Glucose-Stimulated Insulin Secretion. J Biol Chem 2007; 282: 31592-31600.
55. Pralong Wf, Bartley C, Wollheim Cb. Single Islet Beta-Cell Stimulation By Nutrients: Relationship Between Pyridine Nucleotides, Cytosolic Ca2+ And Secretion. Embo J 1990; 9: 53-60.
56. Heart E, Yaney Gc, Corkey Rf, Schultz V, Luc E, Liu L, Deeney Jt, Shirihai O, Tornheim K, Smith Pj, Corkey Be. Ca2+, Nad(P)H And Membrane Potential Changes In Pancreatic Beta-Cells By Methyl Succinate: Comparison With Glucose. Biochem J 2007; 403: 197-205.
57. Freeman H, Shimomura K, Cox Rd, Ashcroft Fm. Nicotinamide Nucleotide Transhydrogenase: A Link Between Insulin Secretion, Glucose Metabolism And Oxidative Stress. Biochem Soc Trans 2006; 34: 806-810.
58. Ivarsson R, Quintens R, Dejonghe S, Tsukamoto K, In 'T Veld P, Renstrom E, Schuit Fc. Redox Control Of Exocytosis: Regulatory Role Of Nadph, Thioredoxin, And Glutaredoxin. Diabetes 2005; 54: 2132-2142.
59. Jitrapakdee S, Wutthisathapornchai A, Wallace Jc, Macdonald Mj. Regulation Of Insulin Secretion: Role Of Mitochondrial Signalling. Diabetologia 2010; 53: 1019-1032.
60. Prentki M, Madiraju Sr. Glycerolipid Metabolism And Signaling In Health And Disease. Endocr Rev 2008; 29: 647-676.
61. Gribble Fm, Proks P, Corkey Be, Ashcroft Fm. Mechanism Of Cloned Atp-Sensitive Potassium Channel Activation By Oleoyl-Coa. J Biol Chem 1998; 273: 26383-26387.
62. Yaney Gc, Corkey Be. Fatty Acid Metabolism And Insulin Secretion In Pancreatic Beta Cells. Diabetologia 2003; 46: 1297-1312.
63. Herrero L, Rubi B, Sebastian D, Serra D, Asins G, Maechler P, Prentki M, Hegardt Fg. Alteration Of The Malonyl-Coa/Carnitine Palmitoyltransferase I Interaction In The Beta-Cell Impairs Glucose-Induced Insulin Secretion. Diabetes 2005; 54: 462-471.
64. Roduit R, Nolan C, Alarcon C, Moore P, Barbeau A, Delghingaro-Augusto V, Przybykowski E, Morin J, Massé F, Massie B, Ruderman N, Rhodes C, Poitout V, Prentki M. A Role For The Malonyl-Coa/Long-Chain Acyl-Coa Pathway Of Lipid Signaling In The Regulation Of Insulin Secretion In Response To Both Fuel And Nonfuel Stimuli. Diabetes 2004; 53: 1007-1019.
65. 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. J Biol Chem 1998; 273: 16146-16154.
66. Kebede Ma, Alquier T, Latour Mg, Poitout V. Lipid Receptors And Islet Function: Therapeutic Implications? Diabetes Obes Metab 2009; 11(Suppl 4): 10-20.
67. Maechler P, Wollheim Cb. Mitochondrial Glutamate Acts As A Messenger In Glucose-Induced Insulin Exocytosis. Nature 1999; 402: 685-689.
68. Vetterli L, Carobbio S, Pournourmohammadi S, Martin-Del-Rio R, Skytt Dm, Waagepetersen Hs, Tamarit-Rodriguez J, Maechler P. Delineation Of Glutamate Pathways And Secretory Responses In Pancreatic Islets With Beta-Cell Specific Abrogation Of The Glutamate Dehydrogenase. Mol Biol Cell 2012; 23: 3851-3862.
69. Li M, Li C, Allen A, Stanley Ca, Smith Tj. The Structure And Allosteric Regulation Of Glutamate Dehydrogenase. Neurochem Int 2011; 59: 445-455.
70. Kibbey Rg, Pongratz Rl, Romanelli Aj, Wollheim Cb, Cline Gw, Shulman Gi. Mitochondrial Gtp Regulates Glucose-Stimulated Insulin Secretion. Cell Metab 2007; 5: 253-264.
71. Wu Zy, Zhu Lj, Zou N, Bombek Lk, Shao Cy, Wang N, Et Al. Ampa Receptors Regulate Exocytosis And Insulin Release In Pancreatic Beta Cells. Traffic 2012; 13: 1124-1139.
72. Russell Ma, Morgan Ng. Expression And Functional Roles Of Guanylate Cyclase Isoforms In Brin-Bd11 ?-Cells. Islets 2010; 2: 374-382.
73. Schulze Du, Dufer M, Wieringa B, Krippeit-Drews P, Drews G. An Adenylate Kinase Is Involved In Katp Channel Regulation Of Mouse Pancreatic Beta Cells. Diabetologia 2007; 50: 2126-2134.
74. Drews G, Krippeit-Drews P, Dufer M. Electrophysiology Of Islet Cells. Adv Exp Med Biol 2010; 654: 115-163.
75. Ruderman N, Prentki M. Amp Kinase And Malonyl-Coa: Targets For Therapy Of The Metabolic Syndrome. Nat Rev Drug Discov 2004; 3: 340-351.
76. Fu A, Eberhard Ce, Screaton Ra. Role Of Ampk In Pancreatic Beta Cell Function. Mol Cell Endocrinol 2013; 366: 127-134.
77. Prentki M, Madiraju Sr. Glycerolipid/Free Fatty Acid Cycle And Islet Beta-Cell Function In Health, Obesity And Diabetes. Mol Cell Endocrinol 2012; 353: 88-100.
78. Lamontagne J, Pepin E, Peyot Ml, Joly E, Ruderman Nb, Poitout V, Madiraju Sr, Nolan Cj, Prentki M. Pioglitazone Acutely Reduces Insulin Secretion And Causes Metabolic Deceleration Of The Pancreatic Beta-Cell At Submaximal Glucose Concentrations. Endocrinology 2009; 150: 3465-3474.
79. Newsholme P, Morgan D, Rebelato E, Oliveiraemilio Hc, Procopio J, Curi R, Carpinelli A. Insights Into The Critical Role Of Nadph Oxidase(S) In The Normal And Dysregulated Pancreatic Beta Cell. Diabetologia 2009; 52: 2489-2498.
80. Pi J, Bai Y, Zhang Q, Wong V, Floering Lm, Daniel K, Reece Jm, Deeney Jt, Andersen Me, Corkey Be, Collins S. Reactive Oxygen Species As A Signal In Glucose-Stimulated Insulin Secretion. Diabetes 2007; 56: 1783-1791.
81. Ma Za, Zhao Z, Turk J. Mitochondrial Dysfunction And Beta-Cell Failure In Type 2 Diabetes Mellitus. Exp Diabetes Res 2012; 2012: 703538.
82. Gehrmann W, Elsner M, Lenzen S. Role Of Metabolically Generated Reactive Oxygen Species For Lipotoxicity In Pancreatic Beta-Cells. Diabetes Obes Metab 2010; 12(Suppl 2): 149-158.
83. 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: 96-102.
84. Crutzen R, Shlyonsky V, Louchami K, Virreira M, Hupkens E, Boom A, Sener A, Malaisse Wj, Beauwens R. Does Nad(P)H Oxidase-Derived H2O2 Participate In Hypotonicity-Induced Insulin Release By Activating Vrac In ?-Cells? Pflugers Arch 2012; 463: 377-390.
85. Robertson Rp, Harmon Js. Pancreatic Islet Beta-Cell And Oxidative Stress: The Importance Of Glutathione Peroxidase. Febs Lett 2007; 581: 3743-3748.
86. Barker Cj, Berggren Po. The Pancreatic Beta Cell As A Paradigm For Advances In Inositide Research. Adv Biol Regul 2012; 52: 361-368.
87. Illies C, Gromada J, Fiume R, Leibiger B, Yu J, Juhl K, Yang Sn, Barma Dk, Falck Jr, Saiardi A, Barker Cj, Berggren Po. Requirement Of Inositol Pyrophosphates For Full Exocytotic Capacity In Pancreatic Beta Cells. Science 2007; 318: 1299-1302.
88. Zhao S, Iglesias J, Mugabo Y, Peyot Ml, Joly E, Madiraju Sr, Prentki M. Monoacylglycerol As A Metabolic Coupling Factor In Glucose-Stimulated Insulin Secretion. Can J Diabetes 2013; 37: 62.
89. Peyot Ml, Guay C, Latour Mg, Lamontagne J, Lussier R, Pineda M, Ruderman Nb, Haemmerle G, Zechner R, Joly E, Madiraju Sr, Poitout V, Prentki M. Adipose Triglyceride Lipase Is Implicated In Fuel-And Non-Fuel-Stimulated Insulin Secretion. J Biol Chem 2009; 284: 16848-16859.
90. Sorhede Winzell M, Ahren B. Glucagon-Like Peptide-1 And Islet Lipolysis. Horm Metab Res 2004; 36: 795-803.
91. Konrad Rj, Major Cd, Wolf Ba. Diacylglycerol Hydrolysis To Arachidonic Acid Is Necessary For Insulin Secretion From Isolated Pancreatic Islets: Sequential Actions Of Diacylglycerol And Monoacylglycerol Lipases. Biochemistry 1994; 33: 13284-13294.
92. Martins Ef, Miyasaka Ck, Newsholme P, Curi R, Carpinelli Ar. Changes Of Fatty Acid Composition In Incubated Rat Pancreatic Islets. Diabetes Metab 2004; 30: 21-27.
93. Sumara G, Formentini I, Collins S, Sumara I, Windak R, Bodenmiller B, Ramracheya R, Caille D, Jiang H, Platt Ka, Meda P, Aebersold R, Rorsman P, Ricci R. Regulation Of Pkd By The Mapk P38Delta In Insulin Secretion And Glucose Homeostasis. Cell 2009; 136: 235-248.
94. Ferdaoussi M, Bergeron V, Zarrouki B, Kolic J, Cantley J, Fielitz J, Olson En, Prentki M, Biden T, Macdonald Pe, Poitout V. G Protein-Coupled Receptor (Gpr)40-Dependent Potentiation Of Insulin Secretion In Mouse Islets Is Mediated By Protein Kinase D1. Diabetologia 2012; 55: 2682-2692.
95. Dzhura I, Chepurny Og, Leech Ca, Roe Mw, Dzhura E, Xu X, Lu Y, Schwede F, Genieser Hg, Smrcka Av, Holz Gg. Phospholipase C-? Links Epac2 Activation To The Potentiation Of Glucose-Stimulated Insulin Secretion From Mouse Islets Of Langerhans. Islets 2011; 3: 121-128.
96. Zhang Cl, Katoh M, Shibasaki T, Minami K, Sunaga Y, Takahashi H, Yokoi N, Iwasaki M, Miki T, Seino S. The Camp Sensor Epac2 Is A Direct Target Of Antidiabetic Sulfonylurea Drugs. Science 2009; 325: 607-610.
97. Giuffrida Fm, Reis Af. Genetic And Clinical Characteristics Of Maturity-Onset Diabetes Of The Young. Diabetes Obes Metab 2005; 7: 318-326.
98. Parikh H, Groop L. Candidate Genes For Type 2 Diabetes. Rev Endocr Metab Disord 2004; 5: 151-176.
99. Rosengren Ah, Braun M, Mahdi T, Andersson Sa, Travers Me, Shigeto M Zhang E, Almgren P, Ladenvall C, Axelsson As, Edlund A, Pedersen Mg, Jonsson A, Ramracheya R, Tang Y, Walker Jn, Barrett A, Johnson Pr, Lyssenko V, Mccarthy Mi, Groop L, Salehi A, Gloyn Al, Renström E, Rorsman P, Eliasson L. Reduced Insulin Exocytosis In Human Pancreatic Beta-Cells With Gene Variants Linked To Type 2 Diabetes. Diabetes 2012; 61: 1726-1733.