TEMPORAL CHANGES IN INSULIN-RESISTANCE AND SECRETION IN 24-H-FASTED CONSCIOUS PREGNANT RATS

To determine the temporal sequence of pregnancy-induced changes in ins ulin action and secretion, awake midpregnant (11-12 days) and late pre gnant (19-20 days) rats underwent a two-step euglycemic hyperinsulinem ic or a hyperglycemic clamp study after a 24-h fast. During euglycemia , insulin-stimulated increments in glucose uptake and clearance in mid pregnant rats were reduced by 60-70% at the lower dose (insulin approx imately 360 pM) and by 20-30% at the higher dose (insulin approximatel y 1,750 pM; P < 0.01 vs. virgin controls). Insulin action was also dim inished in late pregnant rats. However, the magnitude of resistance di d not increase. Insulin-mediated suppression of glucose production was only minimally impaired in midpregnancy. In contrast, glucose product ion was virtually unchanged in late pregnancy, even at the highest ins ulin dose. During hyperglycemia, insulin responses in late pregnancy w ere markedly increased 5-fold above controls and 2.5-fold above midpre gnant rats (P < 0.05). We conclude that rat pregnancy is characterized by the early appearance of peripheral insulin resistance. As pregnanc y progresses toward term, marked hepatic insulin resistance and insuli n hypersecretion develop, whereas peripheral insulin resistance demons trates negligible changes. These data imply that insulin hypersecretio n during late pregnancy is most closely linked to hepatic insulin resi stance, at least in 24-h-fasted animals.