The renin-angiotensin system in streptozotocin-induced diabetes mellitus in the rat

Judith E. Kalinyak, Leonardo A. Sechi, Chandi A. Griffin, Burl R Don, Kamran Tavangar, Frederick B. Kraemer, Andrew R. Hoffman, Morris Schambelan

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

It has been hypothesized that the renin-angiotensin system plays a pathophysiologic role in the renal hemodynamic abnormalities that occur in diabetes mellitus and thereby contributes to the development of diabetic nephropathy. In this study, the tissue-specific regulation of renin and angiotensinogen mRNA levels and the abundance of glomerular angiotensin II receptors were examined in male Sprague-Dawley rats (160 to 240 g) made diabetic with streptozotocin. One subgroup of diabetic rats remained untreated, whereas a second diabetic subgroup received twice-daily doses of insulin to ameliorate hyperglycemia. Animals were euthanized 2 wk after the induction of diabetes. Mean plasma glucose levels at the time of euthanasia were significantly elevated in the untreated diabetic animals when compared with controls or insulin-treated diabetic rats. Weight gain was similar in control and insulin-treated diabetic rats, whereas the untreated diabetic rats gained significantly less. Plasma renin concentration did not differ between control, diabetic, and insulin-treated diabetic groups. In the kidney, no significant differences were found in either angiotensinogen or renin mRNA levels in diabetic animals, whereas glomerular angiotensin II receptors were significantly less abundant in untreated rats as compared with control or insulin-treated diabetic subgroups. Angiotensinogen mRNA levels were significantly lower in the livers and adrenals of diabetic rats in comparison to those in controls and insulin-treated diabetic rats, whereas angiotensinogen mRNA levels in the brain remained unaltered. Although it was demonstrated that angiotensinogen mRNA levels are regulated in a tissue-specific manner, no evidence was found for the activation of the systemic or renal renin-angiotensin system in diabetic animals and, in fact, it was found that the glomerular angiotensin II receptor number was decreased.

Original languageEnglish (US)
Pages (from-to)1337-1345
Number of pages9
JournalJournal of the American Society of Nephrology
Volume4
Issue number6
StatePublished - Dec 1993
Externally publishedYes

Keywords

  • Glomerulus
  • Hyperglycemia
  • mRNA
  • Receptor
  • Renal

ASJC Scopus subject areas

  • Nephrology

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  • Cite this

    Kalinyak, J. E., Sechi, L. A., Griffin, C. A., Don, B. R., Tavangar, K., Kraemer, F. B., Hoffman, A. R., & Schambelan, M. (1993). The renin-angiotensin system in streptozotocin-induced diabetes mellitus in the rat. Journal of the American Society of Nephrology, 4(6), 1337-1345.