Ja. Petterson et al., PREGNANCY AND UNDERNUTRITION ALTER GLUCOSE METABOLIC RESPONSES TO INSULIN IN SHEEP, The Journal of nutrition, 123(7), 1993, pp. 1286-1295
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.