INHIBITORY EFFECT OF PREGNANCY ON COUNTERREGULATORY HORMONE RESPONSESTO HYPOGLYCEMIA IN AWAKE RAT

Intensive insulin treatment during diabetic pregnancy is complicated b y maternal hypoglycemia. To investigate whether pregnancy may contribu te as an independent hypoglycemia risk factor, awake pregnant rats tha t were near term underwent stepped insulin hypoglycemic (3.4 and 2.3 m M) clamp studies in the fasted and nonfasted states. In the fasted sta te, the glucagon response to hypoglycemia was completely suppressed in the pregnant rats (P < 0.01). Epinephrine, but not norepinephrine, wa s also diminished by approximately 70-75% at both hypoglycemic steps, and more exogenous glucose was needed to maintain hypoglycemia during pregnancy. To avoid the potential confounding effect of increased keto ne levels (beta-hydroxybutyrate was approximately 170% higher in the p regnant rats), experiments were repeated in the nonfasting state when ketosis was eliminated in both groups. The nonfasted pregnant rats con tinued to show near complete suppression of the glucagon response, eve n at glucose levels of 2.3 mM. In contrast, a brisk response occurred in nonpregnant controls when glucose fell to 3.4 mM. Although epinephr ine levels in the pregnant rats were also markedly suppressed during t he milder hypoglycemic stimulus, they approached values seen in nonpre gnant controls when glucose was lowered further to 2.3 mM. We conclude d that in the rat, pregnancy markedly suppresses glucagon responses to hypoglycemia. The release of epinephrine, but not norepinephrine, is also blunted, especially during mild hypoglycemia. These findings sugg est that pregnancy may impair glucose counterregulation by inhibiting glucagon and epinephrine release during hypoglycemia.