Abstract: | Recent studies suggest that C-peptide stimulates glucose transport in isolated skeletal muscle. In order to determine the effect of C-peptide on whole body glucose utilization, streptozotocin (60 mg kg-1) (STZ)-induced diabetic and normal rats were studied using the euglycaemic clamp procedure and continuous infusion of somatostatin (1.0 μg kg-1 min-1) in pentobarbital-anaesthetized rats. Plasma insulin levels during the 6.0- and 30.0-mU kg-1 min-1 insulin infusions rose to 70–90 μU mL-1 and 500–700 μU mL-1, respectively. Blood glucose concentrations were clamped at 7.5–7.9 mmol L-1 in the diabetic rats and at basal levels or 7.7 mmol L-1 in the non-diabetic (normal) rats. Biosynthetic human C-peptide (0.5 nmol kg-1 min-1) was infused in 12 diabetic and 11 normal rats, resulting in concentrations of 26–41 nmol L-1. The metabolic clearance rate of glucose (MCR) for the diabetic rats receiving C-peptide (12.0±1.0 mL kg-1 min-1) was significantly (P<0.01) higher than that in the diabetic rats given saline (6.3±0.7 mL kg-1 min-1) or a randomly scrambled C-peptide (7.8±1.3 mL kg-1 min-1) at low-dose insulin infusion but not at the high-dose insulin infusion. In normal rats C-peptide did not significantly increase the MCR for glucose. These results thus demonstrate that C-peptide has the capacity to increase glucose utilization in STZ-induced diabetic rats. |