Acta Diabetologica

, Volume 28, Issue 3–4, pp 193–198 | Cite as

Fat-induced changes in mouse pancreatic islet insulin secretion, insulin biosynthesis and glucose metabolism

  • K. Capito
  • S. E. Hansen
  • C. J. Hedeskov
  • H. Islin
  • P. Thams
Originals

Abstract

Insulin secretion, insulin biosynthesis and islet glucose oxidation were studied in pancreatic islets isolated from fat-fed diabetic mice of both sexes. Insulin secretion from isolated islets was studied after consecutive stimulation with α-ketoisocaproic acid + glutamine, glucose, forskolin, and 12-O-tetradecanoylphorbol 13-acetate. Glucose-induced insulin secretion was impaired in islets from fat-fed mice. This was associated with a reduction of approximately 50% in islet glucose oxidation. Islet insulin secretion stimulated by the non-carbohydrate secretagogues tended to be higher in the fat-fed mice, but a statistically significant effect was not observed. Pancreatic insulin content was reduced by 50%, whereas the islet insulin and DNA content was unchanged after fat feeding. Proinsulin mRNA was reduced by 35% in islets from fat-fed mice, and was associated with a reduction of approximately 50% in glucose-stimulated (pro)insulin biosynthesis. It is concluded that the insulin secretory response of islets isolated from fat-fed mice is similar to the secretory pattern known from human type 2, non-insulin-dependent diabetics, and that a defect in islet glucose recognition, resulting in decreased glucose oxidation, may be responsible for the observed insulin secretory and biosynthetic defects seen after glucose stimulation.

Key words

Type 2, non-insulin-dependent diabetes mellitus Insulin secretion Islet glucose metabolism Insulin biosynthesis Proinsulin mRNA 

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References

  1. 1.
    Newman B, Selby JV, King MC, Slemenda C, Fabsitz R, Friedman GD, Concordance for type 2 (non-insulin-dependent) diabetes mellitus in male twins. Diabetologia 30:763–768, 1987Google Scholar
  2. 2.
    Islin H, Capito K, Hedeskov CJ, Hansen SE, Thams P, The influence of high fat intake on the development of insulin resistance in an animal model for type 2 (non-insulin-dependent) diabetes. Diabetologia 32:498A, 1989Google Scholar
  3. 3.
    Islin H, Capito K, Hansen SE, Hedeskov CJ, Thams P, Ability of omega-3 fatty acids to restore the impaired glucose tolerance in a mouse model for type-2 diabetes. Different effects in male and female mice. Acta Physiol Scand 143:153–160, 1991Google Scholar
  4. 4.
    Bonnevie-Nielsen V, Different effects of high glucose and high fat diet on pancreatic insulin and glucagon in female and male mice. Diabete Metab 8:271–277, 1982Google Scholar
  5. 5.
    Kraegen EW, James DE, Storlien LH, Burleigh KM, Chisholm DJ, In vivo insulin resistance in individual peripheral tissues of the high fat fed rat: assessment by euglycaemic clamp plus deoxyglucose administration. Diabetologia 29:192–198, 1986Google Scholar
  6. 6.
    Storlien LH, James DE, Burleigh KM, Chisholm DJ, Kraeger EW, Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats. Am J Physiol 251:E576-E583, 1986Google Scholar
  7. 7.
    Yamaguchi K, Takashima S, Masuyama T, Matsuoka A, Effects of the electric stress on insulin secretion glucose metabolism in rats fed with a high fat diet. Endocrinol Jpn 25:415–422, 1978Google Scholar
  8. 8.
    DeFronzo RA, The Triumvirate: β-cell, muscle, liver. A Collusion responsible for NIDDM. Diabetes 37:667–687, 1988Google Scholar
  9. 9.
    Pfeifer MA, Halter JB, Porte D Jr, Insulin secretion in diabetes mellitus. Am J Med 70:579–588, 1981Google Scholar
  10. 10.
    Ward WK, Beard JC, Porte D Jr, Clinical aspects of islet B-cell function in non-insulin-dependent diabetes mellitus. Diabetes Metab Rev 2:297–313, 1986Google Scholar
  11. 11.
    Malaisse WJ, Lemonnier D, Malaisse-Lagae F, Mandelbaum F, Secretion and sensitivity to insulin in obese rats fed a high-fat diet. Horm Metab Res 1:9–13, 1968Google Scholar
  12. 12.
    Knudsen P, Kofod H, Lernmark Å, Hedeskov CJ,L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase. Am J Physiol 245:E338-E346, 1983Google Scholar
  13. 13.
    Thams P, Capito K, Hedeskov CJ, An inhibitory role for polyamines in protein kinase C activation and insulin secretion in mouse pancreatic islets. Biochem J 237:131–138, 1986Google Scholar
  14. 14.
    Ashcroft SJH, Bunce J, Lowry M, Hansen SE, Hedeskov CJ, The effects of sugars on (pro)insulin biosynthesis. Biochem J 174:517–526, 1978Google Scholar
  15. 15.
    Grimes A, McArdle HJ, Mercer JFB, A total extract dot blot hybridization procedure for mRNA quantitation in small samples of tissue or cultured cells. Anal Biochem 172:436–443, 1988Google Scholar
  16. 16.
    Khandjiam EW, Optimized hybridization of DNA blotted and fixed to nitrocellulose and nylon membranes. Biotechnology 5:165–167, 1987Google Scholar
  17. 17.
    Trimble ER, Renold AE, Ventral and dorsal areas of rat pancreas: islet hormone content and secretion. Am J Physiol 240:E422-E427, 1981Google Scholar
  18. 18.
    Kissane JM, Robins E, The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J Biol Chem 233:184–188, 1958Google Scholar
  19. 19.
    Berglund O, Lack of glucose-induced priming of insulin release in the perfused pancreas. J Endocrinol 111:185–189, 1987Google Scholar
  20. 20.
    Gepts W, Lecompte PM, The pancreatic islets in diabetes. Am J Med 70:105–114, 1981Google Scholar
  21. 21.
    Giroix MH, Sener A, Bailbe D, Portha B, Malaisse WJ, Impairment of the mitochondrial oxidative response toD-glucose in pancreatic islets from adult rats injected with streptozotocin during the neonatal period. Diabetologia 33:654–660, 1990Google Scholar
  22. 22.
    Welsh N, Hellerström C, In vitro restoration of insulin production in islets from adult rats treated neonatally with streptozotocin. Endocrinology 126:1842–1848, 1990Google Scholar
  23. 23.
    Orland MJ, Permutt MA, Quantitative analysis of pancreatic proinsulin mRNA in gentically diabetic (db/db) mice. Diabetes 36:341–347, 1987Google Scholar
  24. 24.
    Welsh M, Glucose regulation of insulin gene expression. Diabete Metab 15:367–371, 1989Google Scholar
  25. 25.
    Giroix MH, Portha B, Kergoat M, Bailbe D, Picon L, Glucose insensitivity and amino-acid hypersensitivity of insulin release in rats with non-insulin-dependent diabetes. Diabetes 32:445–451, 1983Google Scholar
  26. 26.
    Grill V, Westberg M, Östenson CG, B cell insenitivity in a rat model of non-insulin-dependent diabetes. J Clin Invest 80:664–669, 1987Google Scholar
  27. 27.
    Tsuji K, Taminato T, Usami M, Ishida H, Kitano N, Fukomoto H, Koh G, Kurose T, Yamada Y, Yano H, Seino Y, Imura H, Characteristic features of insulin secretion in the streptozotocin-induced NIDDM rat model. Metabolism 37:1040–1044, 1988Google Scholar
  28. 28.
    Portha B, Giroix MH, Serradas P, Welsh N, Hellerström C, Sener A, Malaisse WJ, Insulin production and glucose metabolism in isolated pancreatic islets of rats with NIDDM. Diabetes 37:1226–1233, 1988Google Scholar
  29. 29.
    Portha B, Decreased glucose-induced insulin release and biosynthesis by islets of rats with non-insulin-dependent diabetes: effect of tissue culture. Endocrinology 117:1735–1741, 1985Google Scholar
  30. 30.
    Giroix MH, Rasschaert J, Bailbe D, Leclercq-Meyer V, Sener A, Portha B, Malaisse WJ, Impairment of glycerol phosphate shuttle in islets from rats with diabetes induced by neonatal streptozocin. Diabetes 40:227–232, 1991Google Scholar
  31. 31.
    Bedoya FJ, Ramirez R, Goberna R, The effect of different kinds of refeeding on islet glucose phosphorylating activites. Metabolism 33:1097–1101, 1984Google Scholar
  32. 32.
    Hedeskov CJ, Capito K, The effect of starvation on insulin secretion and glucose metabolism in mouse pancreatic islets. Biochem J 140:423–433, 1974Google Scholar
  33. 33.
    Randle PJ, Newsholme EA, Garland PB, Regulation of glucose uptake by muscle. 8. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes and starvation on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles. Biochem J 93:652–665, 1964Google Scholar
  34. 34.
    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, 1990Google Scholar
  35. 35.
    Bedoya FJ, Ramirez R, Arilla E, Goberna R, Effect of 2-bromostearate on glucose-phosphorylating activities and the dynamics of insulin secretion in islets of langerhans during fasting. Diabetes 33:858–863, 1984Google Scholar
  36. 36.
    Bolaffi JL, Heldt A, Lewis LD, Grodsky GM, The third phase of in vitro insulin secretion. Evidence for glucose insensitivity. Diabetes 35:370–373, 1986Google Scholar
  37. 37.
    Vague P, Molin JP, The defective glucose sensitivity of the B cell in non insulin dependent diabetes. Improvement after twenty hours of normoglycemia. Metabolism 31:139–142, 1982Google Scholar
  38. 38.
    Portha B, Serradas P, Bailbé D, Suzuki KI, Goto Y, Giroix MH, β-cell insensitivity to glucose in the GK rat, a spontaneous nonobese model for type II diabetes. Diabetes 40:486–491, 1991Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • K. Capito
    • 1
  • S. E. Hansen
    • 1
  • C. J. Hedeskov
    • 1
  • H. Islin
    • 1
  • P. Thams
    • 1
  1. 1.Department of Biochemistry A, The Panum InstituteUniversity of CopenhagenCopenhagen NDenmark

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