INSULIN-LIKE GROWTH-FACTOR-I RESISTANCE IN PERIPHERAL TISSUE BUT NOT IN LIVER IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

The metabolic effect of recombinant human insulin-like growth factor I (IGF-I) was investigated by the glucose clamp technique in normal rat s and streptozotocin-induced diabetic rats, a model of insulin-depende nt diabetes mellitus (IDDM), and compared with that of insulin. Glucos e uptake by peripheral tissues was stimulated by intravenous administr ation of IGF-I at rates of from 0.369 to 3.690 nmol/kg/min in a dose d ependent manner, with a potency of 1/52 that of insulin estimated on t he basis of the ED(50) molar ratio in normal rats. In streptozotocin-i nduced diabetic rats, the maximum effects of IGF-I and insulin were re duced to 72% and 70% of those in normal rats, respectively, indicating the presence of both IGF-I and insulin resistance. Hepatic glucose ou tput in normal rats was suppressed by IGF-I in a dose dependent manner with a weaker potency of 1/99 that of insulin assessed on the basis o f the ED(50) values. In streptozotocin-induced diabetic rats, a dose-r esponse curve of the suppressive effect of insulin on hepatic glucose output shifted to the right, indicating the presence of hepatic insuli n resistance, but a leftward shifting of the suppressive effect of IGF -I on hepatic glucose output was observed. We concluded that the IGF-I effect on peripheral tissue was decreased but that on the liver was r ather increased in streptozotocin-induced diabetic rats, in contrast t o the resistance of both peripheral tissues and liver to insulin.