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. 1986 Aug 1;237(3):807–812. doi: 10.1042/bj2370807

Insulin resistance is accompanied by impairment of amylase-gene expression in the exocrine pancreas of the obese Zucker rat.

E R Trimble, R Bruzzone, D Belin
PMCID: PMC1147060  PMID: 2432875

Abstract

Insulin plays a major role in the control of pancreatic amylase biosynthesis. In this study we determined glucose metabolism by pancreatic acini as well as the pancreatic content of both amylase protein and amylase mRNA during development of insulin resistance in the obese Zucker rat. At age 4 weeks there were no abnormalities detected in the above parameters, although the obese animals were already hyperinsulinaemic. At 6 weeks glucose metabolism was decreased by 50% in acini from obese rats, whereas pancreatic amylase-gene expression was only slightly impaired. At 22 weeks glucose metabolism was decreased by 50%, amylase content by 55% and amylase mRNA by 60% in acinar tissue of obese rats. As expected, hyperinsulinaemia increased markedly with age. Thus development of severe insulin resistance was associated with impairment of amylase-gene expression. To decrease insulin resistance, one group of adult obese rats was treated with Ciglitazone for 4 weeks. A lowered plasma insulin concentration without alteration of food intake was taken as evidence of decreased insulin resistance. This was associated with normalization of glucose metabolism and a marked increase of both amylase content of pancreatic tissue and amylase mRNA. In conclusion, both the increase of insulin resistance with age and its partial reversal by Ciglitazone treatment appear to modulate pancreatic amylase-gene expression in the obese Zucker rat.

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Selected References

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  1. Bazin R., Lavau M. Diet composition and insulin effect on amylase to lipase ratio in pancreas of diabetic rats. Digestion. 1979;19(6):386–391. doi: 10.1159/000198399. [DOI] [PubMed] [Google Scholar]
  2. Bazin R., Lavau M. Effects of high-fat diet on glucose metabolism in isolated pancreatic acini of rats. Am J Physiol. 1982 Dec;243(6):G448–G454. doi: 10.1152/ajpgi.1982.243.6.G448. [DOI] [PubMed] [Google Scholar]
  3. Beckmann J., Holze S., Lenzen S., Panten U. Quantification of cells in islets of Langerhans using DNA determination. Acta Diabetol Lat. 1981;18(1):51–57. doi: 10.1007/BF02056106. [DOI] [PubMed] [Google Scholar]
  4. Belin D., Godeau F., Vassalli J. D. Tumor promoter PMA stimulates the synthesis and secretion of mouse pro-urokinase in MSV-transformed 3T3 cells: this is mediated by an increase in urokinase mRNA content. EMBO J. 1984 Aug;3(8):1901–1906. doi: 10.1002/j.1460-2075.1984.tb02065.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  6. Bruzzone R., Halban P. A., Gjinovci A., Trimble E. R. A new, rapid, method for preparation of dispersed pancreatic acini. Biochem J. 1985 Mar 1;226(2):621–624. doi: 10.1042/bj2260621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bruzzone R., Trimble E. R., Gjinovci A., Renold A. E. Changes in content and secretion of pancreatic enzymes in the obese Zucker rat. Biochem J. 1984 Apr 1;219(1):333–336. doi: 10.1042/bj2190333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chang A. Y., Wyse B. M., Gilchrist B. J. Ciglitazone, a new hypoglycemic agent. II. Effect on glucose and lipid metabolisms and insulin binding in the adipose tissue of C57BL/6J-ob/ob and -+/? mice. Diabetes. 1983 Sep;32(9):839–845. doi: 10.2337/diab.32.9.839. [DOI] [PubMed] [Google Scholar]
  9. Crettaz M., Prentki M., Zaninetti D., Jeanrenaud B. Insulin resistance in soleus muscle from obese Zucker rats. Involvement of several defective sites. Biochem J. 1980 Feb 15;186(2):525–534. doi: 10.1042/bj1860525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cunningham J. J., Calles-Escandon J., Garrido F., Carr D. B., Bode H. H. Hypercorticosteronuria and diminished pituitary responsiveness to corticotropin-releasing factor in obese Zucker rats. Endocrinology. 1986 Jan;118(1):98–101. doi: 10.1210/endo-118-1-98. [DOI] [PubMed] [Google Scholar]
  11. Danielsson A., Marklund S., Stigbrand T. Effects of starvation and islet hormones on the synthesis of amylase in isolated exocrine pancreas of the mouse. Acta Hepatogastroenterol (Stuttg) 1974 Aug;21(4):289–297. [PubMed] [Google Scholar]
  12. Dobberstein B., Blobel G. Functional interaction of plant ribosomes with animal microsomal membranes. Biochem Biophys Res Commun. 1977 Feb 21;74(4):1675–1682. doi: 10.1016/0006-291x(77)90637-4. [DOI] [PubMed] [Google Scholar]
  13. Dranginis A., Morley M., Nesbitt M., Rosenblum B. B., Meisler M. H. Independent regulation of nonallelic pancreatic amylase genes in diabetic mice. J Biol Chem. 1984 Oct 10;259(19):12216–12219. [PubMed] [Google Scholar]
  14. Fujita T., Sugiyama Y., Taketomi S., Sohda T., Kawamatsu Y., Iwatsuka H., Suzuoki Z. Reduction of insulin resistance in obese and/or diabetic animals by 5-[4-(1-methylcyclohexylmethoxy)benzyl]-thiazolidine-2,4-dione (ADD-3878, U-63,287, ciglitazone), a new antidiabetic agent. Diabetes. 1983 Sep;32(9):804–810. doi: 10.2337/diab.32.9.804. [DOI] [PubMed] [Google Scholar]
  15. Giorgi D., Bernard J. P., Lapointe R., Dagorn J. C. Regulation of amylase messenger RNA concentration in rat pancreas by food content. EMBO J. 1984 Jul;3(7):1521–1524. doi: 10.1002/j.1460-2075.1984.tb02005.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Harding J. D., Przybyla A. E., MacDonald R. J., Pictet R. L., Rutter W. J. Effects of dexamethasone and 5-bromodeoxyuridine on the synthesis of amylase mRNA during pancreatic development in vitro. J Biol Chem. 1978 Oct 25;253(20):7531–7537. [PubMed] [Google Scholar]
  17. Kirsch D. M., Bachmann W., Häring H. U. Ciglitazone reverses cAMP-induced post-insulin receptor resistance in rat adipocytes in vitro. FEBS Lett. 1984 Oct 15;176(1):49–54. doi: 10.1016/0014-5793(84)80909-6. [DOI] [PubMed] [Google Scholar]
  18. Kobayashi M., Iwasaki M., Ohgaku S., Maegawa H., Watanabe N., Shigeta Y. A new potentiator of insulin action. Post-receptor activation in vitro. FEBS Lett. 1983 Oct 31;163(1):50–53. doi: 10.1016/0014-5793(83)81160-0. [DOI] [PubMed] [Google Scholar]
  19. Korc M., Owerbach D., Quinto C., Rutter W. J. Pancreatic islet-acinar cell interaction: amylase messenger RNA levels ar determined by insulin. Science. 1981 Jul 17;213(4505):351–353. doi: 10.1126/science.6166044. [DOI] [PubMed] [Google Scholar]
  20. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  21. Le Marchand Y., Freychet P., Jeanrenaud B. Longitudinal study on the establishment of insulin resistance in hypothalamic obese mice. Endocrinology. 1978 Jan;102(1):74–85. doi: 10.1210/endo-102-1-74. [DOI] [PubMed] [Google Scholar]
  22. Lee P. C., Brooks S., Lebenthal E. Effect of fasting and refeeding on pancreatic enzymes and secretagogue responsiveness in rats. Am J Physiol. 1982 Mar;242(3):G215–G221. doi: 10.1152/ajpgi.1982.242.3.G215. [DOI] [PubMed] [Google Scholar]
  23. Logsdon C. D., Moessner J., Williams J. A., Goldfine I. D. Glucocorticoids increase amylase mRNA levels, secretory organelles, and secretion in pancreatic acinar AR42J cells. J Cell Biol. 1985 Apr;100(4):1200–1208. doi: 10.1083/jcb.100.4.1200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McLaughlin C. L., Peikin S. R., Baile C. A. Decreased pancreatic CCK receptor binding and CCK-stimulated amylase release in Zucker obese rats. Physiol Behav. 1984 Jun;32(6):961–965. doi: 10.1016/0031-9384(84)90286-5. [DOI] [PubMed] [Google Scholar]
  25. Rall L., Pictet R., Githens S., Rutter W. J. Glucocorticoids modulate the in vitro development of the embryonic rat pancreas. J Cell Biol. 1977 Nov;75(2 Pt 1):398–409. doi: 10.1083/jcb.75.2.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schibler U., Tosi M., Pittet A. C., Fabiani L., Wellauer P. K. Tissue-specific expression of mouse alpha-amylase genes. J Mol Biol. 1980 Sep 5;142(1):93–116. doi: 10.1016/0022-2836(80)90208-9. [DOI] [PubMed] [Google Scholar]
  27. Schick J., Kern H., Scheele G. Hormonal stimulation in the exocrine pancreas results in coordinate and anticoordinate regulation of protein synthesis. J Cell Biol. 1984 Nov;99(5):1569–1574. doi: 10.1083/jcb.99.5.1569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schick J., Verspohl R., Kern H., Scheele G. Two distinct adaptive responses in the synthesis of exocrine pancreatic enzymes to inverse changes in protein and carbohydrate in the diet. Am J Physiol. 1984 Dec;247(6 Pt 1):G611–G616. doi: 10.1152/ajpgi.1984.247.6.G611. [DOI] [PubMed] [Google Scholar]
  29. Schneeman B. O., Inman M. D., Stern J. S. Pancreatic enzyme activity in obese and lean Zucker rats: a developmental study. J Nutr. 1983 Apr;113(4):921–925. doi: 10.1093/jn/113.4.921. [DOI] [PubMed] [Google Scholar]
  30. Söling H. D., Unger K. O. The role of insulin in the regulation of -amylase synthesis in the rat pancreas. Eur J Clin Invest. 1972 Jun;2(4):199–212. doi: 10.1111/j.1365-2362.1972.tb00645.x. [DOI] [PubMed] [Google Scholar]
  31. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Trimble E. R., Bruzzone R. Abnormalities of caerulein- and carbamylcholine-stimulated pancreatic enzyme secretion in the obese Zucker rat. Regul Pept. 1985 Jul;11(3):227–235. doi: 10.1016/0167-0115(85)90054-0. [DOI] [PubMed] [Google Scholar]
  33. Trimble E. R., Bruzzone R., Gjinovci A., Renold A. E. Activity of the insulo-acinar axis in the isolated perfused rat pancreas. Endocrinology. 1985 Sep;117(3):1246–1252. doi: 10.1210/endo-117-3-1246. [DOI] [PubMed] [Google Scholar]
  34. Trimble E. R., Bruzzone R., Herberg L. Abnormalities of pancreatic exocrine function in obesity: studies in the obese mouse. Comp Biochem Physiol A Comp Physiol. 1986;83(2):387–390. doi: 10.1016/0300-9629(86)90593-1. [DOI] [PubMed] [Google Scholar]
  35. Trimble E. R., Halban P. A., Wollheim C. B., Renold A. E. Functional differences between rat islets of ventral and dorsal pancreatic origin. J Clin Invest. 1982 Feb;69(2):405–413. doi: 10.1172/JCI110464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. White B. A., Bancroft F. C. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem. 1982 Aug 10;257(15):8569–8572. [PubMed] [Google Scholar]
  37. Wicker C., Puigserver A., Scheele G. Dietary regulation of levels of active mRNA coding for amylase and serine protease zymogens in the rat pancreas. Eur J Biochem. 1984 Mar 1;139(2):381–387. doi: 10.1111/j.1432-1033.1984.tb08017.x. [DOI] [PubMed] [Google Scholar]

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