PREGNANCY AND UNDERNUTRITION ALTER GLUCOSE METABOLIC RESPONSES TO INSULIN IN SHEEP

Nonpregnant and late-pregnant ditocous ewes were fed either to maintai n zero energy balance in maternal tissues (fed) or at 50% of this leve l (underfed) for several weeks. Whole-body kinetics of glucose metabol ism were measured under basal conditions, and the hyperinsulinemic, eu glycemic clamp technique was used to define insulin-dose response prof iles for several indices of whole-body glucose utilization, and for en dogenous glucose production. Pregnancy increased and undernutrition de creased basal glucose entry rate (GER), glucose metabolic clearance ra te (GMCR) and insulin-independent glucose utilization (IIGU). The cons istent increment in IIGU of pregnant over nonpregnant ewes was compara ble to previous estimates of uterine glucose uptake. Pregnancy resulte d in higher plasma concentration for 50% maximal responses (ED50) to i nsulin of GER, GMCR, steady-state glucose infusion rate (SSGIR) to mai ntain euglycemia and insulin-dependent glucose utilization (IDGU). The se changes were especially large in underfed pregnant ewes. Effects on the maximal response to insulin of these variables (R(max)) were rela tively small (GMCR, IDGU) or nonsignificant (GER, SSGIR). Maximum insu lin-induced suppression of endogenous glucose production was significa ntly lower due to undernutrition; neither R(max) nor ED50 for this res ponse was affected by pregnancy. Insulin resistance in late-pregnant e wes is primarily due to decreased insulin sensitivity in (presumably) peripheral tissues, implying an alteration of receptor function or of early postreceptor signal transduction.