Impaired biphasic insulin release in mildly diabetic rats bearing a chronic portal vein catheter.

Using a new technique of chronic portal vein catheterization in freely moving rats, we investigated the insulin release to intravenous (IV) glucose (0.5 g/kg) injection in mildly diabetic (35 mg/kg streptozotocin, IV) rats. In nondiabetic rats, plasma insulin of the portal vein showed a clear biphasic release pattern, which peaked within two min after glucose injection, reached a nadir between three and six min, then began to rise to a second peak between 7 and 10 min, and reached a second nadir at 14 min. In mildly diabetic rats, a biphasic insulin release was evident, but both the first and the second phase insulin releases were impaired. In spite of this impaired insulin release, glucose intolerance was mild. Simultaneous blood sampling from the portal and peripheral veins after IV glucose injection revealed that diabetic rats showed diminished hepatic insulin extraction. These results suggest that the biphasic insulin release to glucose is impaired in mildly diabetic rats, but diminished hepatic insulin extraction contributes at least to keeping glucose tolerance mild.