Effects of insulin-like growth factor I on glucose metabolism in rats with liver cirrhosis

Departments of 1 Internal Medicine and 2 Pathology, Yale University School of Medicine, New Haven, Connecticut 06520 To determine the effect of insulin-like growth factor I (IGF-I) on glucose metabolism in cirrhosis, a 2-h euglycemic clamp with IGF-I (0.65 nmol · kg 1 · min 1 ) or insulin (12 pmol · kg 1 · min 1 ) was performed in awake rats with carbon tetrachloride-induced liver cirrhosis. Rates of [3- 3 H]glucose-determined whole body glucose turnover were similar in the fasting state in cirrhotic and control rats (36.4 ± 2.6 and 37.7 ± 2.8 µmol · kg 1 · min 1 , respectively). In the control group, IGF-I and insulin had similar effects on turnover (81.6 ± 27.0 and 76.1 ± 9.9 µmol · kg 1 · min 1 ), muscle glycogen synthesis (47.5 ± 12.3 and 37.5 ± 2.5 nmol · g muscle 1 · min 1 ), and suppression of endogenous glucose production (EGP; 54 ± 14 and 60 ± 12%). Cirrhotic rats were markedly insulin resistant, reflected by a 43% reduction of turnover (43.8 ± 9.4 µmol · g muscle 1 · min 1 ; P = 0.03), a 73% reduction in muscle glycogen synthesis (10.2 ± 3.4 nmol · g muscle 1 · min 1 ; P