In Vitro Effects of Glycosylated Insulin and Glucagon in Perfused Liver of the Rat

Summary

Using perfused liver of the rat, the hepatic uptake of glycosylated insulin (GI) and glucagon (GG) and its effects on hepatic glucose output were investigated. Insulin and glucagon were glycosylated in ambient high glucose concentration, and GI₈₀ or GG₈₀ (insulin or glucagon incubated with 0.08 % glucose), GI₃₅₀ or GG₃₅₀ (incubated with 0.35 % glucose), and GI₁₀₀₀ or GG₁₀₀₀ (incubated with 1% glucose) were prepared. The liver was perfused with the medium containing 1000 μU/ml insulin and 200 pg/ml glucagon or 200 μU/ml insulin and 1000 pg/ml glucagon. The fractional uptake of insulin or glucagon by perfused liver was not significantly altered by the glycosylation. In the liver perfused with 1000 μU/ml insulin and 200 pg/ml glucagon, glucose output was not changed by the glycosylation of the hormones, while in the liver perfused with 200 μU/ml insulin and 1000 pg/ml glucagon, GI₁₀₀₀ reduced its biological activity, as reflected by insulin-mediated decrease in glucose output. These results suggest that in the liver insulin incubated with markedly high concentration of glucose reduces its biological activity at a physiological concentration in the presence of high concentration of glucagon

Key words

Glycosylated Insulin - Glycosylated Glucagon - Perfused Rat Liver - Hepatic Glucose Output