AJP - Regulatory, Integrative and Comparative Physiology, Vol 268, Issue 2 475-R479, Copyright © 1995 by American Physiological Society
Muscarinic stimulation maintains in vivo insulin secretion in response to glucose after prolonged hyperglycemia
B. Balkan and B. E. Dunning
Department of Diabetes, Sandoz Research Institute, Sandoz Pharmaceutical Corporation, East Hanover, New Jersey 07936.
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.
