Chronic exposure to free fatty acid reduces pancreatic β cell insulin content by increasing basal insulin secretion that is not compensated for by a corresponding increase in proinsulin biosynthesis translation

Journal of Clinical Investigation

Volumn 101, Issue 5, 1998, Pages 1094-1101

  Bollheimer, L Cornelius ^a   Skelly, Robert H ^a   Chester, Michael W ^a   McGarry, J Denis ^a   Rhodes, Christopher J ^a,b  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Free fatty acid; Insulin secretion; Non insulin dependent diabetes mellitus (NIDDM); Pancreatic islet; Proinsulin biosynthesis

Indexed keywords

FATTY ACID; GLUCOSE; INSULIN; OLEIC ACID; PROINSULIN;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; INSULIN DEGRADATION; INSULIN RELEASE; INSULIN SYNTHESIS; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PATHOGENESIS; PRIORITY JOURNAL; RAT; TRANSLATION REGULATION;

EID: 0032030866     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI420     Document Type: Article

References (50)

1. Felber, J.P., and A. Vanotti. 1964. Effects of fat infusions on glucose tolerance and insulin plasma levels. Med. Exp. 10:153-156.
2. Madison, L.L., W.A. Seyffert, R.H. Unger, and B. Barker. 1968. Effect of plasma free fatty acids on plasma glucagon and serum insulin concentrations. Metabolism. 17:301-304.
3. Crespin, S.R., W.B. Greenough III, and D. Steinberg. 1969. Stimulation of insulin secretion by infusion of free fatty acids. J. Clin. Invest. 48:1934-1943
4. Goberna, R.J., J.J. Tamrit, R. Fussgänger, J. Tamrit, and E.F. Pfeiffer. 1974. Action of β-hydroxybutyrate. acetoacetate and palmitate on the insulin release from the perfused rat pancreas. Horm. Metab. Res. 6:256-260.
5. Malaisse, W.J., S. Best, F. Kawazu, F. Malaisse-Lagae, and A. Sener. 1983. The stimulus-secretion coupling of glucose-induced insulin release. Fuel metabolism in islets deprived of exogenous nutrients. Arch. Biochem. Biophys. 224:102-110.
6. Stein, D.T., V. Esser, B. Stevenson, K.E. Lane, J.H. Whiteside, M.B. Daniels, S. Chen, and J.D. McGarry. 1996. Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat. J. Clin. Invest. 97: 2728-2735.
7. Stein, D.T., B.E. Stevenson, M.W. Chester, M. Basit, M.B. Daniels, S.D. Turley, and J.D. McGarry. 1997. The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation. J. Clin. Invest. 100:398-403.
8. Prentki, M., S. Vischer, M.C. Glennon, R. Regazzi, J.T. Deeney, and B.E. Corkey. 1992. Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion. J. Biol. Chem. 267:5802-5810.
9. Prentki, M., and B.E. Corkey. 1996. Are mulonyl-CoA and cytosolic long-chain acyl-CoA esters the key signaling molecules linking multiple tissue defects in obesity and NIDDM? Diabetes. 45:273-283.
10. Groop, L.C., R.C. Bonadonna, E. Ferrannini. and R.A. DeFronzo. 1991. The role of free fatty acid metabolism in the pathogenesis of insulin resistance in obesity and non-insulin-dependent diabetes mellitus. J. Endocrinol Metab. 72:96-107.
11. McGarry, J.D. 1992. What if Minkowski had been ageusic? An alternative angle on diabetes. Science. 259:766-774.
12. Unger, R.H. 1994. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes. 44:863-870.
13. Boden, G. 1997. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes. 46:3-10.
14. McGarry, J.D. 1994. Disordered metabolism in diabetes: have we underemphasized the fat cell component. J. Cell. Biochem. 55(Suppl.):29-38.
15. Sako, Y., and V.E. Grill. 1990. A 48-hour lipid infusion in the rat dependently inhibits glucose-induced insulin secretion and β-cell oxidation through a process likely coupled to fatty acid oxidation. Endocrinology. 127:1580-1589.
16. Elks, M.L. 1993. Chronic perifusion of rat islets with palmitate suppresses glucose-stimulated insulin release. Endocrinology. 133:208-214.
17. Zhou, Y.P., and V.E. Grill. 1994. 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.
18. Lee, Y., H. Hirose, M. Ohneda, J.H. Johnson, J.D. McGarry, and R.H. Linger. 1994. β-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-β-cell relationships. Proc. Natl. Acad. Sci. USA. 91:10878-10882.
19. Milburn, J.L., H. Hirose, Y.H. Lee, A. Nagasawa, M. Ogawa, H. Ohneda, H. BeltrandelRio, C.B. Newgard, J.H. Johnson, and R.H. Unger, 1995. Pancreatic β-cells in obesity: evidence for induction of functional morphologic and metabolic abnormalities by increased long-chain fatty acids. J. Biol. Chem. 270:1295-1299.
20. Zhou, Y.P., and V.E. Grill. 1995. Palmitate induced β-cell sensitivity to glucose is coupled to decreased pyruvate dehydrogenase activity in rat pancreatic islets. Diabetes. 44:394-399.
21. Hirose, H., Y.H. Lee, L.R. Inman, Y. Nagasawa, J.H. Johnson, and R.H. Unger. 1996. Defective fatty acid mediated β-cell-compensation in Zucker diabetic fatty rats. J. Biol. Chem. 271:5633-5637.
22. Orci, L. 1985. The insulin factory: a tour of the plant surroundings and a visit to the assembly line. Diabetologia. 28:528-546.
23. Rhodes, C.J. 1996. Processing of the insulin molecule. In Diabetes Mellitus. A Fundamental and Clinical Text. D. LeRoith, S.I. Taylor, and J.M. Olefsky, editors. Lippincott-Raven Publishers, Philadelphia. 27-41.
24. Pipeleers, D.G., M. Marichal, and W.J. Malaisse. 1973. The stimulus coupling of glucose-induced insulin release. XIV. Glucose regulation of insular biosynthetic activity. Endocrinology. 93:1001-1011.
25. Ashcroft, S.J.H. 1480. Glucoreceptor mechanisms and the control of insulin release and biosynthesis. Diabetologia. 18:5-15.
26. Itoh, N., and H. Okamoto. 1980. Translational control of proinsulin synthesis by glucose. Nature. 283:100-102.
27. Alarcón, C., B. Lincoln, and C.J. Rhodes. 1993. The biosynthesis of the subtilisin-related proprotein covertase PC3. but not that of the PC2 convertase. is regulated by glucose in parallel to proinsulin biosynthesis in rat pancreatic islets. J. Biol. Chem. 268(6):4276-4280.
28. Skelly, R.H., L.C. Bollheimer, B.L. Wicksteed, B.E. Corkey, and C.J. Rhodes. 1998. A distinct difference in the metabolic stimulus-response coupling pathways fro regulating proinsulin biosynthesis and insulin secretion that lies at the level of a requirement for fatty acyl moieties. Biochem. J. In press.
29. Rhodes, C.J., and P.A. Halban. 1487. Newly-synthesized proinsulin/insulin and stored insulin are released from pancreatic B-cells via a regulated, rather than a constitutive pathway. J. Cell Biol. 105:145-153.
30. Olszewski, S., J.T. Deeney, G.T. Schuppin, K.P. Williams, B.E. Corkey, and C.J. Rhodes. 1944. Rab3A effector domain peptides induce insulin exocytosis via a specific interaction with a cytosolic protein doublet. J. Biol. Chem. 269:27987-27991.
31. Skelly, R.H., G.T. Schuppin, H. Ishihara, Y. Oka. and C.J. Rhodes. 1996. Glucose-regulated translational control of proinsulin biosynthesis with that of the proinsulin endopeptidases PC2 and PC3 in the insulin-producing MIN6 cell line. Diabetes. 45:37-43.
32. Alarcón, C., J.L. Leahy, G.T. Schuppin, and C.J. Rhodes. 1995. Hyperproinsulinemia in a glucose-infusion rat model of non insulin dependent diabetes mellitus is a symptom of increased secretory demand rather than a defect in the proinsulin conversion mechanism. J. Clin. Invest. 95:1032-1039.
33. Schuppin, G.T., and C.J. Rhodes. 1995. Specific coordinated regulation of PC3 and PC2 gene transcription with that of preproinsulin in insulin-producing βTC3 cells. Biochcm. J. 313:259-268.
34. Andersson, A. 1976. Tissue culture of isolated pancreatic islets. Acta Endocrinol. 205:283-294.
35. Andersson, A., K. Asplund, and R. Larkins. 1978. Insulin production by pancreatic islets if obese hyperglycemic mice cultured for one week in different glucose concentrations. Acta Physiol. Scand. 104:377-385.
36. Welsh, M., D.A. Nielsen, A.J. MacKrell, and D.F. Steiner. 1985. Control of insulin gene expression in pancreatic β-cells and in an insulin-producing cell line. RIN-5F cells. 2. Regulation of insulin mRNA stability. J. Biol. Chem. 260: 13590-13594.
37. Welsh, N., and C. Hellerström. 1990. Effects of tissue culture on insulin production in islets from rats treated neonatally with streptozotocin. Endocrinology. 126:1842-1848.
38. Olson, S.E., A. Andersson, B. Peterson, and C. Hellerström. 1976. Effects of somatostatin on the biosynthesis and release of insulin from isolated pancreatic islets. Diabets. Metab. Rev. 2:199-202.
39. Reaven, G.M., C. Hollenbeck, C.Y. Jeng, M.S. Wu, and Y.D. Chen. 1988. Measurement of plasma glucose, free fatty acid, lactate and insulin for 24h in patients with NIDDM. Diabetes. 37:1020-1024.
40. Boden, G., X. Chen, J. Rosner, and M. Barton. 1994. Effects of 48h fat infusion on insulin secretion and glucose utilization. Diabetes. 44:1239-1242.
41. Kenned, G.C., and M. German. 1996. Insulin gene regulation. In Diabetes Mellitus. A Fundamental and Clinical Text. D. LcRoith, S.I. Taylor, and J.M. Olefsky. editors. Lippincott-Raven Publishers. Philadelphia. 20-26.
42. Docherty, K., and A.R. Clark. 1994. Nutrient regulation of insulin gene expression. FASEB J. 8:20-27.
43. Permutt, M.A., K. Kakita, P. Malinas, I. Karl, S. Bonner-Weir, G. Weir, and S.J. Giddings. 1984. An in vivo analysis of pancreatic protein and insulin biosynthesis in a rat model for non-insulin dependent diabetes. J. Clin. Invest. 73:1344-1350.
44. Welsh, M., N. Scherberg, R. Gilmore, and D.F. Steiner. 1986. Translational control of insulin biosynthesis. Evidence for regulation of elongation, initiation and signal-recognition-particle-mediated translational arrest by glucose. Biochem. J. 235:459-467.
45. Harris, M.I., W.C. Hadden, W.C. Knowler, and P.H. Bennett. 1987. Prevalence of diabetes, impaired glucose tolerance and plasma glucose levels in US population aged 20-74 years. Diabetes. 36:523-534.
46. Horton, E.S. 1995. NIDDM-the devastating disease. Diabetes Res. Clin. Pract. 28(Suppl.):3-11.
47. Clark, A., E.J. de Konig, A.T. Hattersley, B.C. Hansen, C.S. Yajnik, and J. Poulton. 1995. Pancreatic pathology in non-insulin dependent diabetes (NIDDM). Diabetes Res. Clin. Pract. 28:39-17.
48. Leahy, J.L. 1990. Natural History of B-cell Dysfunction in NIDDM. Diabetes Care. 13:992-1010.
49. Leahy, J.L., S. Bonner-Weir, and G.C. Weir. 1992. β-cell dysfunction by chronic hyperglycemia: current ideas on mechanism of glucose-induced insulin secretion. Diabetes Care. 15:442-154.
50. Rhodes, C.J. and C. Alarcón. 1994. What β-cell defect could lead to hyperproinsulinemia in NIDDM: some clues from recent advances made in understanding the proinsulin conversion mechanism. Diabetes. 43:511-517.