Effects of C-peptide on glomerular and renal size and renal function in diabetic rats

Abstract

Strict glycemic control and antihypertensive treatment may decrease but not eliminate the risk of progressive nephropathy in diabetic patients. C-peptide has been shown to exert beneficial effects on complications, including incipient nephropathy, in type 1 diabetes. Renal effects of 14 days of intravenous infusion of C-peptide or NaCl (placebo) were studied in three groups of rats: one nondiabetic NaCl-treated (normal, N = 7), one streptozotocin diabetic NaCl-treated (D-placebo, N = 7), and one streptozotocin diabetic C-peptide-treated group (D-C-p, N = 7). Metabolic data and albuminuria were measured in metabolic cages every fourth day. After 14 days, the glomerular filtration rate (GFR) was measured by inulin clearance and available renal functional reserve (RFR) by glycine infusion, whereupon one kidney was perfusion fixed for morphological studies. Glucose levels were 36.7 +/- 1.3 and 34.0 +/- 1.7 mmol/L in the D-placebo and D-C-p groups, respectively. The D-placebo group presented a 32% (P < 0.001) larger glomerular volume than the D-C-p group. The D-placebo group also presented a significantly larger renal weight than the normal group in contrast to the D-C-p group. Urinary albumin excretion increased in the D-placebo group in contrast to the other groups. GFR was 1.72 +/- 0.12 mL/min (normal), 3.73 +/- 0.19 mL/min (D-placebo, P < 0.001 vs. normal) and 2.16 +/- 0.16 mL/min (D-C-p, nonsignificant vs. normal). Available RFR was 93 +/- 25% (normal), 10 +/- 4% (D-placebo, P < 0.05 vs. normal) and 57 +/- 13% (D-C-p, nonsignificant vs. normal) of basal GFR. Physiological doses of homologous C-peptide prevent the development of glomerular hypertrophy, albuminuria, and glomerular hyperfiltration in rats with experimentally induced diabetes.