TY - JOUR
T1 - Inhibitory effect of pregnancy on counterregulatory hormone responses to hypoglycemia in awake rat
AU - Rossi, G.
AU - Lapaczewski, P.
AU - Diamond, Michael Peter
AU - Jacob, R. J.
AU - Shulman, G. I.
AU - Sherwin, R. S.
PY - 1993
Y1 - 1993
N2 - 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 ~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 (β-hydroxybutyrate was ~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.
AB - 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 ~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 (β-hydroxybutyrate was ~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.
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U2 - 10.2337/diab.42.10.1440
DO - 10.2337/diab.42.10.1440
M3 - Article
C2 - 8375583
AN - SCOPUS:0027183273
SN - 0012-1797
VL - 42
SP - 1440
EP - 1445
JO - Diabetes
JF - Diabetes
IS - 10
ER -