Rat C peptide I and II stimulate glucose utilization in STZ-induced diabetic rats

Aims. To study the effects of physiological concentrations of rat proinsulin C peptide I and II, respectively, on whole body glucose utilization in streptozotocin diabetic and healthy rats. Methods. A sequential insulin clamp procedure was used (insulin infusion rates 3.0 and 30.0mU.kg(-1).min(-1)) in awake animals. C-peptide infusion rates were 0.05 and 0.5 nmol kg(-1) min(-1). Blood glucose was clamped at 7.7 +/- 0.3 mmol/l in the diabetic rats and at 3.9 +/- 0.1 mmol/l in the healthy rats. Results. In diabetic rats infused at lower rates of C peptide and insulin, glucose utilization increased by 79-90 % (p < 0.001) compared with diabetic animals infused with saline and insulin. Increasing the rate of C-peptide infusion tenfold did not elicit a statistically significant further increase in glucose utilization. C peptide I and II exerted similar effects. The metabolic clearance rate for glucose in the diabetic animals infused with C peptide was not different from that of the healthy rats. During high-dose insulin infusion (30.0 mU kg(-1) min(-1)) glucose utilization increased considerably and no statistically significant C-peptide effects were observed. About 85 % of the increase in glucose utilization induced by C peptide could be blocked by treatment with N-monomethyl-L-arginine. Conclusions/interpretation. Physiological concentrations of homologous C peptide stimulate whole body glucose utilization in diabetic but not in healthy rats. C peptide I and II elicit similar effects. The influence of C peptide on glucose utilization may be mediated by nitric oxide.