Muscarinic stimulation maintains in vivo insulin secretion in response to glucose after prolonged hyperglycemia.
Prolonged hyperglycemia impairs the in vitro insulin release by islets of Langerhans in response to glucose but exaggerates the in vivo insulin response. We hypothesized that this discrepancy results from increased vagal stimulation of the islets. Conscious chronically cannulated rats were infused with glucose (15 mg/min) or saline for 48 h. Three hours thereafter, an intravenous glucose tolerance test was performed with or without prior injection of atropine (0.2 mg). Atropine markedly (> 70%) reduced the insulin response in glucose-infused, but not in saline-infused, rats. Glucose-infused rats displayed basal hypoglycemia but normal glucose excursions during an intravenous glucose tolerance test. It is concluded that prolonged hyperglycemia produces exaggerated muscarinic activation of the beta-cells that will persist > or = 3 h after the termination of the glucose infusion and normalizes in vivo insulin secretion. It is possible that increased parasympathetic activation of the pancreas might constitute a general mechanism to maintain insulin output when the demand for insulin exceeds the inherent beta-cell responsiveness.
Balkan
B
B
Department of Diabetes, Sandoz Research Institute, Sandoz Pharmaceutical Corporation, East Hanover, New Jersey 07936.
Dunning
B E
BE
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D018727:Muscarinic Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
D018678:Cholinergic Agents; D007328:Insulin; D018727:Muscarinic Antagonists; D012965:Sodium Chloride; D001285:Atropine; D002217:Carbachol; D005947:Glucose