Intensive
insulin treatment during diabetic pregnancy is complicated by maternal
hypoglycemia. To investigate whether pregnancy may contribute as an independent
hypoglycemia risk factor, awake pregnant rats that were near term underwent stepped
insulin hypoglycemic (3.4 and 2.3 mM) clamp studies in the fasted and nonfasted states. In the fasted state, the
glucagon response to
hypoglycemia was completely suppressed in the pregnant rats (P < 0.01).
Epinephrine, but not
norepinephrine, was 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
ketone levels (
beta-hydroxybutyrate was approximately 170% higher in the pregnant rats), experiments were repeated in the nonfasting state when
ketosis was eliminated in both groups. The nonfasted pregnant rats continued to show near complete suppression of the
glucagon response, even at
glucose levels of 2.3 mM. In contrast, a brisk response occurred in nonpregnant controls when
glucose fell to 3.4 mM. Although
epinephrine levels in the pregnant rats were also markedly suppressed during the milder
hypoglycemic stimulus, they approached values seen in nonpregnant controls when
glucose was lowered further to 2.3 mM. We concluded 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 suggest that pregnancy may impair
glucose counterregulation by inhibiting
glucagon and
epinephrine release during
hypoglycemia.