Lipid-induced pancreatic β-cell dysfunction: Focus on in vivo studies

American Journal of Physiology - Endocrinology and Metabolism

Volumn 300, Issue 2, 2011, Pages

  Giacca, Adria ^a   Xiao, Changting ^a   Oprescu, Andrei I ^a   Carpentier, Andre C ^b   Lewis, Gary F ^a  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITÉ DE SHERBROOKE   (Canada)

Author keywords

cell function; Insulin secretion

Indexed keywords

4 PHENYLBUTYRIC ACID; ACETYLCYSTEINE; ANTIOXIDANT; APOCYNIN; BISPEROXOVANADIUM; FATTY ACID; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; LIPID; PROTEIN TYROSINE PHOSPHATASE INHIBITOR; SALICYLIC ACID; TAURINE; TEMPOL; UNCLASSIFIED DRUG;

CELL DEATH; DRUG BIOAVAILABILITY; DRUG MECHANISM; ENDOPLASMIC RETICULUM STRESS; FAMILY HISTORY; FATTY ACID BLOOD LEVEL; FIRST PASS EFFECT; GENETIC PREDISPOSITION; GLUCOSE BLOOD LEVEL; GLUCOSE INTOLERANCE; HUMAN; IN VIVO STUDY; INSULIN RELEASE; INSULIN SENSITIVITY; LIPID DIET; LIPOTOXICITY; LOADING DRUG DOSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OXIDATIVE STRESS; PANCREAS DISEASE; PANCREAS ISLET BETA CELL; PANCREAS ISLET CELL FUNCTION; PANCREAS ISLET DISEASE; PRIORITY JOURNAL; REVIEW;

ANIMALS; CELL DEATH; DIABETES MELLITUS; DIETARY FATS; FATTY ACIDS, NONESTERIFIED; GENETIC PREDISPOSITION TO DISEASE; HUMANS; INSULIN-SECRETING CELLS; LIPIDS; OBESITY; PANCREATIC DISEASES;

EID: 79251585927     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00416.2010     Document Type: Review

References (98)

1. Ahren B, Gudbjartsson T, Al-Amin AN, Martensson H, Myrsen-Axcrona U, Karlsson S, Mulder H, Sundler F. Islet perturbations in rats fed a high-fat diet. Pancreas 18: 75-83, 1999. (Pubitemid 29011340)
2. Azevedo-Martins AK, Lortz S, Lenzen S, Curi R, Eizirik DL, Tiedge M. Improvement of the mitochondrial antioxidant defense status prevents cytokine-induced nuclear factor-kappaB activation in insulin-producing cells. Diabetes 52: 93-101, 2003. (Pubitemid 36042112)
3. Bajaj M, Suraamornkul S, Kashyap S, Cusi K, Mandarino L, De-Fronzo RA. Sustained reduction in plasma free fatty acid concentration improves insulin action without altering plasma adipocytokine levels in subjects with strong family history of type 2 diabetes. J Clin Endocrinol Metab 89: 4649-4655, 2004. (Pubitemid 39244483)
4. Bergman RN, Phillips LS, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest 68: 1456-1467, 1981. (Pubitemid 12194400)
5. Bernal-Mizrachi E, Fatrai S, Johnson JD, Ohsugi M, Otani K, Han Z, Polonsky KS, Permutt MA. Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet beta cells. J Clin Invest 114: 928-936, 2004.
6. Boden G, Chen X, Rosner J, Barton M. Effects of a 48-h fat infusion on insulin secretion and glucose utilization. Diabetes 44: 1239-1242, 1995.
7. Boden G, Chen X, Ruiz J, White JV, Rossetti L. Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest 93: 2438-2446, 1994.
8. Boden G, Ruiz J, Kim CJ, Chen X. Effects of prolonged glucose infusion on insulin secretion, clearance, and action in normal subjects. Am J Physiol Endocrinol Metab 270: E251-E258, 1996.
9. Boni-Schnetzler M, Ehses JA, Faulenbach M, Donath MY. Insulitis in type 2 diabetes. Diabetes Obes Metab 10, Suppl 4: 201-204, 2008.
10. Brassard P, Frisch F, Lavoie F, Cyr D, Bourbonnais A, Cunnane SC, Patterson BW, Drouin R, Baillargeon JP, Carpentier AC. Impaired plasma nonesterified fatty acid tolerance is an early defect in the natural history of type 2 diabetes. J Clin Endocrinol Metab 93: 837-844, 2008.
11. Briaud I, Kelpe CL, Johnson LM, Tran PO, Poitout V. Differential effects of hyperlipidemia on insulin secretion in islets of langerhans from hyperglycemic versus normoglycemic rats. Diabetes 51: 662-668, 2002.
12. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52: 102-110, 2003.
13. 2+, leading to induction of endoplasmic reticulum stress in pancreatic beta-cells. Diabetes 54: 452-461, 2005.
14. Carpentier A, Giacca A, Lewis GF. Effect of increased plasma nonesterified fatty acids (NEFAs) on arginine-stimulated insulin secretion in obese humans. Diabetologia 44: 1989-1997, 2001.
15. Carpentier A, Mittelman SD, Bergman RN, Giacca A, Lewis GF. Prolonged elevation of plasma free fatty acids impairs pancreatic beta-cell function in obese nondiabetic humans but not in individuals with type 2 diabetes. Diabetes 49: 399-408, 2000.
16. Carpentier A, Mittelman SD, Lamarche B, Bergman RN, Giacca A, Lewis GF. Acute enhancement of insulin secretion by FFA in humans is lost with prolonged FFA elevation. Am J Physiol Endocrinol Metab 276: E1055-E1066, 1999. (Pubitemid 29323421)
17. Carpentier A, Zinman B, Leung N, Giacca A, Hanley AJ, Harris SB, Hegele RA, Lewis GF. Free fatty acid-mediated impairment of glucos-estimulated insulin secretion in nondiabetic Oji-Cree individuals from the Sandy Lake community of Ontario, Canada: a population at very high risk for developing type 2 diabetes. Diabetes 52: 1485-1495, 2003.
18. Carpentier AC, Bourbonnais A, Frisch F, Giacca A, Lewis GF. Plasma nonesterified fatty acid intolerance and hyperglycemia are associated with intravenous lipid-induced impairment of insulin sensitivity and disposition index. J Clin Endocrinol Metab 95: 1256-1264, 2010.
19. Carpentier AC, Frisch F, Cyr D, Genereux P, Patterson BW, Giguere R, Baillargeon JP. On the suppression of plasma nonesterified fatty acids by insulin during enhanced intravascular lipolysis in humans. Am J Physiol Endocrinol Metab 289: E849-E856, 2005.
20. Chen NG, Reaven GM. Fatty acid inhibition of glucose-stimulated insulin secretion is enhanced in pancreatic islets from insulin-resistant rats. Metabolism 48: 1314-1317, 1999.
21. Crespin SR, Greenough WB, III, Steinberg D. Stimulation of insulin secretion by long-chain free fatty acids. A direct pancreatic effect. J Clin Invest 52: 1979-1984, 1973.
22. Cusi K. Lessons learned from studying families genetically predisposed to type 2 diabetes mellitus. Curr Diab Rep 9: 200-207, 2009.
23. Cusi K, Kashyap S, Gastaldelli A, Bajaj M, Cersosimo E. Effects on insulin secretion and insulin action of a 48-h reduction of plasma free fatty acids with acipimox in nondiabetic subjects genetically predisposed to type 2 diabetes. Am J Physiol Endocrinol Metab 292: E1775-E1781, 2007.
24. Del GS, Lupi R, Marselli L, Masini M, Bugliani M, Sbrana S, Torri S, Pollera M, Boggi U, Mosca F, Del PS, Marchetti P. Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes 54: 727-735, 2005.
25. Diraison F, Parton L, Ferre P, Foufelle F, Briscoe CP, Leclerc I, Rutter GA. Over-expression of sterol-regulatory-element-binding protein-1c (SREBP1c) in rat pancreatic islets induces lipogenesis and decreases glucose-stimulated insulin release: modulation by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR). Biochem J 378: 769-778, 2004.
26. Dobbins RL, Chester MW, Daniels MB, McGarry JD, Stein DT. Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans. Diabetes 47: 1613-1618, 1998.
27. Dobbins RL, Szczepaniak LS, Myhill J, Tamura Y, Uchino H, Giacca A, McGarry JD. The composition of dietary fat directly influences glucose-stimulated insulin secretion in rats. Diabetes 51: 1825-1833, 2002.
28. Dubois M, Kerr-Conte J, Gmyr V, Bouckenooghe T, Muharram G, D'Herbomez M, Martin-Ponthieu A, Vantyghem MC, Vandewalle B, Pattou F. Non-esterified fatty acids are deleterious for human pancreatic islet function at physiological glucose concentration. Diabetologia 47: 463-469, 2004.
29. Ehses JA, Meier DT, Wueest S, Rytka J, Boller S, Wielinga PY, Schraenen A, Lemaire K, Debray S, Van LL, Pospisilik JA, Tschopp O, Schultze SM, Malipiero U, Esterbauer H, Ellingsgaard H, Rutti S, Schuit FC, Lutz TA, Boni-Schnetzler M, Konrad D, Donath MY. Toll-like receptor 2-deficient mice are protected from insulin resistance and beta cell dysfunction induced by a high-fat diet. Diabetologia 53: 1795-1806, 2010.
30. Ehses JA, Perren A, Eppler E, Ribaux P, Pospisilik JA, Maor-Cahn R, Gueripel X, Ellingsgaard H, Schneider MK, Biollaz G, Fontana A, Reinecke M, Homo-Delarche F, Donath MY. Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56: 2356-2370, 2007. (Pubitemid 47358243)
31. Fernandez-Real JM, Lopez-Bermejo A, Ropero AB, Piquer S, Nadal A, Bassols J, Casamitjana R, Gomis R, Arnaiz E, Perez I, Ricart W. Salicylates increase insulin secretion in healthy obese subjects. J Clin Endocrinol Metab 93: 2523-2530, 2008.
32. Ghosh S, Baltimore D. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. Nature 344: 678-682, 1990.
33. Goh TT, Mason TM, Gupta N, So A, Lam TK, Lam L, Lewis GF, Mari A, Giacca A. Lipid-induced β-cell dysfunction in vivo in models of progressive β-cell failure. Am J Physiol Endocrinol Metab 292: E549-E560, 2007.
34. 2+ homeostasis in β-cells. Am J Physiol Endocrinol Metab 296: E690-E701, 2009.
35. Hagman DK, Latour MG, Chakrabarti SK, Fontes G, Amyot J, Tremblay C, Semache M, Lausier JA, Roskens V, Mirmira RG, Jetton TL, Poitout V. Cyclical and alternating infusions of glucose and intralipid in rats inhibit insulin gene expression and Pdx-1 binding in islets. Diabetes 57: 424-431, 2008.
36. Harmon JS, Bogdani M, Parazzoli SD, Mak SS, Oseid EA, Berghmans M, Leboeuf RC, Robertson RP. Beta-cell-specific overexpression of glutathione peroxidase preserves intranuclear MafA and reverses diabetes in db/db mice. Endocrinology 150: 4855-4862, 2009.
37. Hennes MM, Dua A, Kissebah AH. Effects of free fatty acids and glucose on splanchnic insulin dynamics. Diabetes 46: 57-62, 1997.
38. Hennige AM, Ranta F, Heinzelmann I, Dufer M, Michael D, Braumuller H, Lutz SZ, Lammers R, Drews G, Bosch F, Haring HU, Ullrich S. Overexpression of kinase-negative protein kinase Cdelta in pancreatic beta-cells protects mice from diet-induced glucose intolerance and beta-cell dysfunction. Diabetes 59: 119-127, 2010.
39. Hull RL, Andrikopoulos S, Verchere CB, Vidal J, Wang F, Cnop M, Prigeon RL, Kahn SE. Increased dietary fat promotes islet amyloid formation and beta-cell secretory dysfunction in a transgenic mouse model of islet amyloid. Diabetes 52: 372-379, 2003.
40. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49: 1939-1945, 2000.
41. 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 51: 3211-3219, 2002.
42. Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42: 1663-1672, 1993.
43. Kaneto H, Kajimoto Y, Miyagawa J, Matsuoka T, Fujitani Y, Umayahara Y, Hanafusa T, Matsuzawa Y, Yamasaki Y, Hori M. Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 48: 2398-2406, 1999.
44. Kaneto H, Matsuoka TA, Nakatani Y, Kawamori D, Miyatsuka T, Matsuhisa M, Yamasaki Y. Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes. J Mol Med 83: 429-439, 2005. (Pubitemid 40922165)
45. Kashyap S, Belfort R, Gastaldelli A, Pratipanawatr T, Berria R, Pratipanawatr W, Bajaj M, Mandarino L, DeFronzo R, Cusi K. A sustained increase in plasma free fatty acids impairs insulin secretion in nondiabetic subjects genetically predisposed to develop type 2 diabetes. Diabetes 52: 2461-2474, 2003.
46. Kiely A, Robinson A, McClenaghan NH, Flatt PR, Newsholme P. Toll-like receptor agonist induced changes in clonal rat BRIN-BD11 beta-cell insulin secretion and signal transduction. J Endocrinol 202: 365-373, 2009.
47. Koulajian K, Barbuto R, Tang C, Oprescu AI, Giacca A. Apocynin, an NADPH oxidase inhibitor, partially restores the secretory capacity of the beta cells after prolonged (48h) oleate infusion. Diabetes 56: A1448, 2009.
48. Kulkarni RN. Receptors for insulin and insulin-like growth factor-1 and insulin receptor substrate-1 mediate pathways that regulate islet function. Biochem Soc Trans 30: 317-322, 2002.
49. Kunisaki M, Bursell SE, Umeda F, Nawata H, King GL. Normalization of diacylglycerol-protein kinase C activation by vitamin E in aorta of diabetic rats and cultured rat smooth muscle cells exposed to elevated glucose levels. Diabetes 43: 1372-1377, 1994.
50. Lacraz G, Giroix MH, Kassis N, Coulaud J, Galinier A, Noll C, Cornut M, Schmidlin F, Paul JL, Janel N, Irminger JC, Kergoat M, Portha B, Donath MY, Ehses JA, Homo-Delarche F. Islet endothelial activation and oxidative stress gene expression is reduced by IL-1Ra treatment in the type 2 diabetic GK rat. PLoS One 4: e6963, 2009.
51. Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 356: 1517-1526, 2007.
52. Latour MG, Alquier T, Oseid E, Tremblay C, Jetton TL, Luo J, Lin DC, Poitout V. GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo. Diabetes 56: 1087-1094, 2007.
53. Leung N, Sakaue T, Carpentier A, Uffelman K, Giacca A, Lewis GF. Prolonged increase of plasma non-esterified fatty acids fully abolishes the stimulatory effect of 24 hours of moderate hyperglycaemia on insulin sensitivity and pancreatic beta-cell function in obese men. Diabetologia 47: 204-213, 2004.
54. Lopez-Bergami P, Ronai Z. Requirements for PKC-augmented JNK activation by MKK4/7. Int J Biochem Cell Biol 40: 1055-1064, 2008.
55. Lupi R, Del GS, Fierabracci V, Marselli L, Novelli M, Patane G, Boggi U, Mosca F, Piro S, Del PS, Marchetti P. Lipotoxicity in human pancreatic islets and the protective effect of metformin. Diabetes 51, Suppl 1: S134-S137, 2002.
56. Magnan C, Collins S, Berthault MF, Kassis N, Vincent M, Gilbert M, Penicaud L, Ktorza A, Assimacopoulos-Jeannet F. Lipid infusion lowers sympathetic nervous activity and leads to increased beta-cell responsiveness to glucose. J Clin Invest 103: 413-419, 1999. (Pubitemid 29069992)
57. Magnan C, Cruciani C, Clement L, Adnot P, Vincent M, Kergoat M, Girard A, Elghozi JL, Velho G, Beressi N, Bresson JL, Ktorza A. Glucose-induced insulin hypersecretion in lipid-infused healthy subjects is associated with a decrease in plasma norepinephrine concentration and urinary excretion. J Clin Endocrinol Metab 86: 4901-4907, 2001.
58. Marchetti P, Bugliani M, Lupi R, Marselli L, Masini M, Boggi U, Filipponi F, Weir GC, Eizirik DL, Cnop M. The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients. Diabetologia 50: 2486-2494, 2007. (Pubitemid 350060637)
59. Mason TM, Goh T, Tchipashvili V, Sandhu H, Gupta N, Lewis GF, Giacca A. Prolonged elevation of plasma free fatty acids desensitizes the insulin secretory response to glucose in vivo in rats. Diabetes 48: 524-530, 1999. (Pubitemid 29106865)
60. Matveyenko AV, Butler PC. Relationship between beta-cell mass and diabetes onset. Diabetes Obes Metab 10, Suppl 4: 23-31, 2008.
61. Matveyenko AV, Gurlo T, Daval M, Butler AE, Butler PC. Successful versus failed adaptation to high-fat diet-induced insulin resistance: the role of IAPP-induced beta-cell endoplasmic reticulum stress. Diabetes 58: 906-916, 2009.
62. Nolan CJ, Madiraju MS, Delghingaro-Augusto V, Peyot ML, Prentki M. Fatty acid signaling in the beta-cell and insulin secretion. Diabetes 55, Suppl 2: S16-S23, 2006. (Pubitemid 44927028)
63. Oprescu AI, Bikopoulos G, Naassan A, Allister EM, Tang C, Park E, Uchino H, Lewis GF, Fantus IG, Rozakis-Adcock M, Wheeler MB, Giacca A. Free fatty acid-induced reduction in glucose-stimulated insulin secretion: evidence for a role of oxidative stress in vitro and in vivo. Diabetes 56: 2927-2937, 2007. (Pubitemid 350223627)
64. Oprescu AI, Han P, Lewis GF, Giacca A. Bisperoxovanadate prevents FFA-induced β-cell dysfunction in vitro and in vivo (Abstract). Diabetes 56: A386, 2007.
65. Owyang AM, Maedler K, Gross L, Yin J, Esposito L, Shu L, Jadhav J, Domsgen E, Bergemann J, Lee S, Kantak S. XOMA 052, an anti-IL-1(beta) monoclonal antibody, improves glucose control and (beta)-cell function in the diet-induced obesity mouse model. Endocrinology 151: 2515-2527, 2010.
66. Ozcan U, Yilmaz E, Ozcan L, Furuhashi M, Vaillancourt E, Smith RO, Gorgun CZ, Hotamisligil GS. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 313: 1137-1140, 2006.
67. Paolisso G, Gambardella A, Amato L, Tortoriello R, D'Amore A, Varricchio M, D'Onofrio F. Opposite effects of short- and long-term fatty acid infusion on insulin secretion in healthy subjects. Diabetologia 38: 1295-1299, 1995.
68. Paolisso G, Tagliamonte MR, Rizzo MR, Gualdiero P, Saccomanno F, Gambardella A, Giugliano D, D'Onofrio F, Howard BV. Lowering fatty acids potentiates acute insulin response in first degree relatives of people with type II diabetes. Diabetologia 41: 1127-1132, 1998.
69. Patane G, Piro S, Rabuazzo AM, Anello M, Vigneri R, Purrello F. Metformin restores insulin secretion altered by chronic exposure to free fatty acids or high glucose: a direct metformin effect on pancreatic beta-cells. Diabetes 49: 735-740, 2000.
70. Pi J, Bai Y, Daniel KW, Liu D, Lyght O, Edelstein D, Brownlee M, Corkey BE, Collins S. Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function. Endocrinology 150: 3040-3048, 2009.
71. Poitout V, Robertson RP. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev 29: 351-366, 2008.
72. Qvigstad E, Mostad IL, Bjerve KS, Grill VE. Acute lowering of circulating fatty acids improves insulin secretion in a subset of type 2 diabetes subjects. Am J Physiol Endocrinol Metab 284: E129-E137, 2003.
73. + channels. Diabetes 54: 2070-2079, 2005.
74. Sako Y, Grill VE. 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: 1580-1589, 1990.
75. Sauter NS, Schulthess FT, Galasso R, Castellani LW, Maedler K. The antiinflammatory cytokine interleukin-1 receptor antagonist protects from high-fat diet-induced hyperglycemia. Endocrinology 149: 2208-2218, 2008.
76. Schmitz-Peiffer C, Laybutt DR, Burchfield JG, Gurisik E, Narasimhan S, Mitchell CJ, Pedersen DJ, Braun U, Cooney GJ, Leitges M, Biden TJ. Inhibition of PKCepsilon improves glucose-stimulated insulin secretion and reduces insulin clearance. Cell Metab 6: 320-328, 2007.
77. Shimabukuro M, Higa M, Zhou YT, Wang MY, Newgard CB, Unger RH. Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression. J Biol Chem 273: 32487-32490, 1998.
78. Shimabukuro M, Ohneda M, Lee Y, Unger RH. Role of nitric oxide in obesity-induced beta cell disease. J Clin Invest 100: 290-295, 1997.
79. Shimabukuro M, Zhou YT, Lee Y, Unger RH. Troglitazone lowers islet fat and restores beta cell function of Zucker diabetic fatty rats. J Biol Chem 273: 3547-3550, 1998.
80. Sone H, Kagawa Y. Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice. Diabetologia 48: 58-67, 2005.
81. Staiger H, Machicao F, Fritsche A, Haring HU. Pathomechanisms of type 2 diabetes genes. Endocr Rev 30: 557-585, 2009.
82. Stefan N, Wahl HG, Fritsche A, Haring H, Stumvoll M. Effect of the pattern of elevated free fatty acids on insulin sensitivity and insulin secretion in healthy humans. Horm Metab Res 33: 432-438, 2001.
83. Steil GM, Trivedi N, Jonas JC, Hasenkamp WM, Sharma A, Bonner-Weir S, Weir GC. Adaptation of β-cell mass to substrate oversupply: enhanced function with normal gene expression. Am J Physiol Endocrinol Metab 280: E788-E796, 2001. (Pubitemid 33774949)
84. Stein DT, Esser V, Stevenson BE, Lane KE, Whiteside JH, Daniels MB, Chen S, McGarry JD. Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat. J Clin Invest 97: 2728-2735, 1996. (Pubitemid 26197087)
85. Steneberg P, Rubins N, Bartoov-Shifman R, Walker MD, Edlund H. The FFA receptor GPR40 links hyperinsulinemia, hepatic steatosis, and impaired glucose homeostasis in mouse. Cell Metab 1: 245-258, 2005. (Pubitemid 43960613)
86. Storgaard H, Jensen CB, Vaag AA, Volund A, Madsbad S. Insulin secretion after short- and long-term low-grade free fatty acid infusion in men with increased risk of developing type 2 diabetes. Metabolism 52: 885-894, 2003.
87. Stumvoll M, Goldstein BJ, van Haeften TW. Pathogenesis of type 2 diabetes. Endocr Res 32: 19-37, 2007.
88. Tang C, Ehses JA, Donath MY, Giacca A. Interleukin-1 receptor antagonist prevents fat-induced β-cell dysfunction in diabetes-prone Bio-Breeding rats (Abstract). Diabetes 59: A62, 2010.
89. Vandewalle B, Moerman E, Lefebvre B, Defrance F, Gmyr V, Lukowiak B, Kerr CJ, Pattou F. PPARgamma-dependent and -independent effects of rosiglitazone on lipotoxic human pancreatic islets. Biochem Biophys Res Commun 366: 1096-1101, 2008.
90. Warnotte C, Gilon P, Nenquin M, Henquin JC. Mechanisms of the stimulation of insulin release by saturated fatty acids. A study of palmitate effects in mouse beta-cells. Diabetes 43: 703-711, 1994.
91. Xiao C, Giacca A, Lewis GF. Sodium phenylbutyrate, a drug with known capacity to reduce endoplasmic reticulum stress, alleviates lipid-induced insulin resistance and beta-cell dysfunction in humans. Diabetes In Revision, 2010.
92. Xiao C, Giacca A, Carpentier A, Lewis GF. Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucosestimulated insulin secretion, sensitivity and clearance in overweight and obese, non-diabetic humans. Diabetologia 49: 1371-1379, 2006.
93. Xiao C, Giacca A, Lewis GF. Oral taurine but not N-acetylcysteine ameliorates NEFA-induced impairment in insulin sensitivity and beta cell function in obese and overweight, non-diabetic men. Diabetologia 51: 139-146, 2008.
94. Xiao C, Giacca A, Lewis GF. Effect of high-dose sodium salicylate on chronically elevated plasma nonesterified fatty acid-induced insulin resistance and β-cell dysfunction. Am J Physiol Endocrinol Metab 297: E1205-E1211, 2009.
95. Yamamoto M, Yamato E, Toyoda S, Tashiro F, Ikegami H, Yodoi J, Miyazaki J. Transgenic expression of antioxidant protein thioredoxin in pancreatic beta cells prevents progression of type 2 diabetes mellitus. Antioxid Redox Signal 10: 43-49, 2008.
96. Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature 454: 455-462, 2008.
97. Zhang X, Ke L, Yu Y. Elevated circulating FFA levels causing pancreatic islet cell dysfunction through oxidative stress. J Endocrinol Invest 2009.
98. Zhou YP, Grill VE. Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle. J Clin Invest 93: 870-876, 1994.