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

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

Research output: Contribution to journalArticle

38 Scopus citations

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)
Pages (from-to)E446-E453
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume265
Issue number3 28-3
DOIs
StatePublished - 1993

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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