Journal of the American Society of Nephrology, Vol 3, 1686-1693, Copyright © 1993 by American Society of Nephrology

REGULAR ARTICLES

Contrasting effects of acute insulin infusion on renal function in awake nondiabetic and diabetic rats

BJ Tucker, MM Mendonca and RC Blantz
Department of Medicine, University of California, School of Medicine, La Jolla 92093-9151.

Glomerular hyperfiltration in established, moderately hyperglycemic, insulin-dependent diabetes has been hypothesized to be the result of mild volume expansion. Because glomerular hyperfiltration in diabetics is normalized by insulin treatment, then insulin treatment should also reduce extracellular fluid or plasma volume. Previous studies have demonstrated that acute insulin treatment in nondiabetic kidneys results in vasodilation and increased GFR. It is possible that stimuli to the diabetic kidney, as a result of insulin-induced fluid shifts that reduce extracellular fluid volume (ECF) via glucose transport, result in reduction in GFR, opposing the direct renal vasodilatory action of insulin. Awake, chronically cannulated Wistar rats were used in both nondiabetic and established, moderately hyperglycemic, streptozotocin diabetic conditions. After the initial measurements of GFR, RPF, and ECF were obtained, insulin R (5 U) was administered acutely, both groups of rats were glucose clamped at euglycemic levels, and the measurements were repeated. In nondiabetic rats, GFR increased from 0.90 +/- 0.04 to 1.12 +/- 0.06 mL/min.100 g body wt after insulin treatment (P < 0.05), whereas in diabetic rats, GFR, which was greater than in the nondiabetic rats (P < 0.05), decreased from 1.37 +/- 0.03 to 1.13 +/- 0.05 mL/min.100 g body wt (P < 0.05) after acute insulin treatment. The alterations in GFR paralleled the changes in RPF, and the GFR alterations are most likely mediated by the changes in RPF. ECF was not different between nondiabetic and diabetic rats (28 +/- 2 versus 26 +/- 2% of body wt, respectively) and was not significantly altered by acute insulin infusion. Therefore, the contrasting effects of insulin infusion on GFR and RPF in nondiabetic versus diabetic rats cannot be attributed to alterations in ECF. In addition, the data demonstrate that ECF expansion is not required to sustain glomerular hyperfiltration.

This article has been cited by other articles:

				V. Vallon, R. C. Blantz, and S. Thomson Glomerular Hyperfiltration and the Salt Paradox in Early Type 1 Diabetes Mellitus: A Tubulo-Centric View J. Am. Soc. Nephrol., February 1, 2003; 14(2): 530 - 537. [Abstract] [Full Text] [PDF]

				S. ISHIZUKA, R. CUNARD, S. POUCELL-HATTON, L. WEAD, M. LORTIE, S. C. THOMSON, F. B. GABBAI, J. SATRIANO, and R. C. BLANTZ Agmatine Inhibits Cell Proliferation and Improves Renal Function in Anti--Thy-1 Glomerulonephritis J. Am. Soc. Nephrol., December 1, 2000; 11(12): 2256 - 2264. [Abstract] [Full Text]

				V. Vallon, M. Albinus, and D. Blach Effect of KATP Channel Blocker U37883A on Renal Function in Experimental Diabetes Mellitus in Rats J. Pharmacol. Exp. Ther., September 1, 1998; 286(3): 1215 - 1221. [Abstract] [Full Text]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673