Amylin-insulin relationships in insulin resistance with and without diabetic hyperglycemia

T. R. Pieber, Daniel T. Stein, A. Ogawa, T. Alam, M. Ohneda, K. McCorkle, L. Chen, J. D. McGarry, R. H. Unger

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

To determine if increased secretion of amylin can be implicated in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) in vitro and in vivo, we studied its relationships to insulin in insulin-resistant rats with and without NIDDM. In obesity-associated and dexamethasone-induced insulin resistance without diabetes, basal and stimulated secretion of amylin and insulin by isolated pancreata were proportionately elevated, leaving the amylin-to-insulin ratio (A/I) unchanged. By contrast, whenever diabetes occurred in dexamethasone-treated rats or in spontaneously diabetic obese insulin-resistant ZDF-drt male rats, a doubling of A/I was invariably observed due to an increase in amylin without a proportional increase in insulin secretion. Correction of dexamethasone-induced hyperglycemia with the glucocorticord receptor antagonist RU-486 was accompanied by a decline in A/I. Longitudinal in vivo studies demonstrated in both spontaneous and dexamethasone-induced models of NIDDM an increase in plasma A/I at the onset of hyperglycemia. In dexamethasone-induced diabetes, the increased A/I was associated with a high proamylin mRNA relative to proinsulin mRNA. We conclude that amylin and insulin expression and secretion rise in concert in compensated insulin-resistant states, but when hyperglycemia is present the increase in amylin exceeds that of insulin. Although a role of an increased A/I in the pathogenesis of NIDDM has not been established directly, these studies indicate that such a role could be possible.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume265
Issue number3 28-3
StatePublished - 1993
Externally publishedYes

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Islet Amyloid Polypeptide
Hyperglycemia
Insulin Resistance
Medical problems
Insulin
Dexamethasone
Type 2 Diabetes Mellitus
Rats
Proinsulin
Mifepristone
Messenger RNA
Pancreas
Obesity

Keywords

  • dexamethasone
  • expression
  • messenger ribonucleic acid
  • mifepristone
  • obesity rat
  • pancreas
  • pancreatic perfusion
  • RU- 486
  • secretion
  • ZDF/drt
  • Zucker

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology

Cite this

Amylin-insulin relationships in insulin resistance with and without diabetic hyperglycemia. / Pieber, T. R.; Stein, Daniel T.; Ogawa, A.; Alam, T.; Ohneda, M.; McCorkle, K.; Chen, L.; McGarry, J. D.; Unger, R. H.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 265, No. 3 28-3, 1993.

Research output: Contribution to journalArticle

Pieber, TR, Stein, DT, Ogawa, A, Alam, T, Ohneda, M, McCorkle, K, Chen, L, McGarry, JD & Unger, RH 1993, 'Amylin-insulin relationships in insulin resistance with and without diabetic hyperglycemia', American Journal of Physiology - Endocrinology and Metabolism, vol. 265, no. 3 28-3.
Pieber, T. R. ; Stein, Daniel T. ; Ogawa, A. ; Alam, T. ; Ohneda, M. ; McCorkle, K. ; Chen, L. ; McGarry, J. D. ; Unger, R. H. / Amylin-insulin relationships in insulin resistance with and without diabetic hyperglycemia. In: American Journal of Physiology - Endocrinology and Metabolism. 1993 ; Vol. 265, No. 3 28-3.
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