GLUCAGON AND GLUCOSE DYNAMICS IN SHEEP - EVIDENCE FOR GLUCAGON RESISTANCE IN THE FETUS

The effects of glucagon infused at 5 and 50 ng .cntdot. kg-1 .cntdot. min-1 on glucose turnover (GT), production (Ra) and utilization (Rd) were compared in fetal (F; n = 5, gestation 129 .+-. 3 days, term .apprx. 150 days) and nonpregnant adult (A; n = 5 and 6) sheep. Infusion of glucagon at 5 ng .cntdot. kg-1 .cntdot. min-1 raised fetal glucagon levels (IRG) from a basal of 168 .+-. 27 to a mean sustained level of 863 .+-. 160 pg/ml but had no effect on basal levels of glucose (G) of 12 .+-. 3 mg/dl, insulin (IRI) of 16 .+-. 3 .mu.U/ml, GT of 21 .+-. 1.3 mg/min and Rd of 15 .+-. 2 mg/min; Ra remained negligible. When fetal IRG was raised to a mean sustained level of 1809 .+-. 210 pg/ml by infusion of glucagon at 50 ng .cntdot. kg-1 .cntdot. min-1, G doubled to 23 .+-. 1.5 mg/dl, IRI rose to 21 .+-. 0.9 .mu.U/ml, GT rose to 60 .+-. 5 mg/min, Rd to 30 .+-. 4.8 mg/min and Ra to 41 .+-. 6 mg/min (P < 0.01 for each) indicating induction of F glucose production so that GT was now derived from endogenous sources. When IRG levels were raised from 109 .+-. 10 to 538 .+-. 43 pg/ml by infusion of 5 ng .cntdot. kg-1 .cntdot. min-1 to A, basal G rose from 56 .+-. 2 to 88 .+-. 6 mg/dl, IRI from 24 .+-. 2 to 45 .+-. 6 .mu.U/ml, GT and Ra from 93 .+-. 7 to 173 .+-. 17 mg/min and Rd from 93 .+-. 7 to 148 .+-. 12 mg/min (P < 0.01 for each). No further increments of these indexes occurred in A when IRG was raised to a mean sustained level of 2275 .+-. 135 pg/ml by infusion of 50 ng .cntdot. kg-1 .cntdot. min-1. Evidently there is a relative resistance in F to the glycemic effects of glucagon, consistent with previously demonstrated decreases of hepatic glucagon receptors and glucagon-stimulated cAMP production in fetal liver.