Contrasting effects of acute insulin infusion on renal function in awake nondiabetic and diabetic rats.
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.
Tucker
B J
BJ
Department of Medicine, University of California, School of Medicine, La Jolla 92093-9151.
Mendonca
M M
MM
Blantz
R C
RC
D000818:Animals; D001783:Blood Flow Velocity; D001810:Blood Volume; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005110:Extracellular Space / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006943:Hyperglycemia / Q000503:physiopathology; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects*; D013311:Streptozocin; D013997:Time Factors; D014666:Vasomotor System / Q000187:drug effects; D014851:Wakefulness
D007328:Insulin; D013311:Streptozocin