Gender difference in the glucagon response to glucopenic stress in mice.
A gender difference in the glucagon response to insulin-induced hypoglycemia was previously demonstrated in humans. Whether this reflects a gender difference in autonomic activation or in pancreatic alpha-cell regulation is not known. We investigated the glucagon, epinephrine, and norepinephrine responses to neuroglycopenic stress induced by 2-deoxy-D-glucose (2-DG) or insulin in female and male mice. 2-DG increased plasma glucagon levels by 559 +/- 68% in females versus 281 +/- 46% in males (P < 0.01). Plasma levels of epinephrine or norepinephrine after 2-DG administration did not differ between genders. During insulin-induced hypoglycemia, the glucagon response was similarly higher in females (P < 0.001), whereas the plasma catecholamine response was higher in males (P < 0.05). In vivo, the glucagon response to carbachol or clonidine was higher in females (P < 0.05). In isolated islets, the glucagon response to carbachol (100 microM; P = 0.003) but not to clonidine (1 microM) was larger in females. We conclude that in addition to a larger alpha-cell mass (previously described in female mice), an increased sensitivity of the glucagon-producing alpha-cell to cholinergic activation contributes to the larger glucagon response to glucopenic stress in female mice.
Karlsson
Sven
S
Department of Medicine, Lund University, SE-221 84 Lund, Sweden. Sven.Karlsson@med.lu.se
Scheurink
Anton J W
AJ
Ahrén
Bo
B
D000311:Adrenal Glands / Q000502:physiology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood* / Q000378:metabolism; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009638:Norepinephrine / Q000097:blood; D012727:Sex Characteristics; D013312:Stress, Physiological / Q000378:metabolism; D013565:Sympatholytics / Q000494:pharmacology
D000963:Antimetabolites; D001786:Blood Glucose; D018679:Cholinergic Agonists; D007004:Hypoglycemic Agents; D007328:Insulin; D013565:Sympatholytics; D002217:Carbachol; D005934:Glucagon; D003847:Deoxyglucose; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine