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

Background. Strict glycemic control and antihypertensive treatment may decr ease but not eliminate the risk of progressive nephropathy in diabetic pati ents. C-peptide has been shown to exert beneficial effects on complications . including incipient nephropathy, in type 1 diabetes. Methods. Renal effects of 14 days of intravenous infusion of C-peptide or N aCl (placebo) were studied in three groups of rats: one nondiabetic NaCl-tr eated (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 albumineuria were measured in metabolic cages ever y fourth day. After 14 days, the glomerular filtration rate (GFR) was measu red by inulin clearance and available renal functional reserve (RFR) by gly cine infusion, whereupon one kidney was perfusion fixed for morphological s tudies. Results. Glucose levels were 36.7 +/- 13 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 g roup also presented a significantly larger renal weight than the normal gro up in contrast to the D-C-p group. Urinary albumin excretion increased in t he D-placebo group in contrast to the other groups. GFR was 1.72 +/- 0.12 m L/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 wa s 93 +/- 25% (normal). 10 +/- 4% (D-placebo, P < 0.05 vs. normal) and 57 +/ - 13% (D-C-p. nonsignificant vs. normal) of basal GFR. Conclusions. Physiological doses of homologous C-peptide prevent the develo pment of glomerular hypertrophy, albuminuria, and glomerular hyperfiltratio n in rats with experimentally induced diabetes.