Glucagon secretion and autonomic signaling during hypoglycemia in late pregnancy.
We examined net pancreatic norepinephrine (NE) spillover, pancreatic polypeptide (PP) release, and the decrement in C-peptide to identify factors involved in the blunted counterregulatory glucagon response in pregnancy. Conscious pregnant [pregnant hypoglycemic (Ph); 3rd trimester; n = 8] and nonpregnant [nonpregnant hypoglycemic (NPh); n = 6] dogs were studied during insulin-induced (approximately 12-fold basal insulin concentrations) hypoglycemia (plasma glucose 3.1 mM). Additional dogs were studied during hyperinsulinemic euglycemia [nonpregnant euglycemic (NPe), n = 4; pregnant euglycemic (Pe), n = 5; plasma glucose 6 mM]. Arterial glucagon concentrations declined similarly in NPe and Pe. Areas under the curve (AUCs) of the changes in glucagon and epinephrine were seven- and threefold greater in NPh than Ph (P < 0.05 between groups for both). Glucagon secretion fell below basal in NPe, Pe, and Ph but rose significantly in NPh. C-peptide declined 0.25 +/- 0.06, 0.12 +/- 0.11, 0.28 +/- 0.05, and 0.13 +/- 0.02 ng/ml in NPe, Pe, NPh, and Ph, respectively (P < 0.05, NPh vs. Ph). AUCs of NE spillover were 516 +/- 274, 265 +/- 303, 506 +/- 94, and -63 +/- 79 ng, respectively (P < 0.05, NPh vs. Ph). The AUC of PP release was approximately threefold greater in NPh than Ph (P < 0.05) but not different between euglycemic groups. The current evidence strongly suggests that the blunting of glucagon secretion during insulin-induced hypoglycemia in pregnancy is related to generalized impairment of a number of different signals, including parasympathetic and sympathoadrenal stimuli and altered sensing of circulating and/or intraislet insulin.
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.
Kathryn M
KM
Canniff
Marta S
MS
Smith
D Brooks
DB
Lacy
Phillip E
PE
Williams
Mary Courtney
MC
Moore
D000818:Animals; D001341:Autonomic Nervous System / Q000378:metabolism*; D001786:Blood Glucose / Q000502:physiology; D004285:Dogs; D005260:Female; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D015309:Glucose Clamp Technique; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D010179:Pancreas / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D011374:Progesterone; D005934:Glucagon