Glucagon secretory response to hypoglycaemia, adrenaline and carbachol in streptozotocin-diabetic rats

B. Ahren, J. S. Stern, R. L. Gingerich, D. L. Curry, Peter J Havel

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Glucagon response to insulin-induced hypoglycaemia is impaired in diabetes, but the mechanism is not established. Pancreatic A cell hyporesponsiveness to adrenergic or cholinergic stimulation could contribute to the impairment. We therefore compared the plasma glucagon responses to intravenous infusion of adrenaline (1200 ng kg-1 min-1 for 20 min) or to intravenous injection of the cholinergic agonist carbachol (50 μg kg-1) in chloral hydrate-anaesthetized rats made diabetic with the use of streptozotocin (80 mg kg-1 subcutaneously) 6 weeks before and in anaesthetized control rats. Insulin was infused intravenously to reduce plasma glucose levels to below 1.8 mmol L-1. As expected, the plasma glucagon response was reduced by ~ 45% in streptozotocin-diabetic rats compared with controls (P = 0.045). During adrenaline infusion, plasma glucagon levels increased by 277 ± 92 pg mL-1 in controls (P=0.009) and by 570 ± 137 pg mL-1 in the diabetic rats (P = 0.002). Thus, the plasma glucagon response to adrenaline was approximately doubled in the diabetic rats (P = 0.045). Following carbachol injection, plasma glucagon levels were raised by 1211 ± 208 pg mL-1 (P < 0.001) in controls but only by 555 ± 242 pg mL-1 in the diabetic rats (P = 0.049). Thus, the plasma glucagon response to carbachol was impaired by ~ 58% in the diabetic rats (P = 0.028). We conclude that carbachol-stimulated glucagon secretion is impaired concomitantly with the impaired glucagon response to hypoglycaemia in streptozotocin-diabetic rats, whereas adrenaline-induced glucagon secretion is exaggerated. We suggest that a reduced pancreatic A cell responsiveness to cholinergic stimulation could contribute to the impairment of the glucagon response to insulin-induced hypoglycaemia in diabetes.

Original languageEnglish (US)
Pages (from-to)215-221
Number of pages7
JournalActa Physiologica Scandinavica
Volume155
Issue number2
StatePublished - 1995

Keywords

  • Adrenaline
  • Cholinergic
  • Diabetes
  • Glucagon secretion
  • Hypoglycaemia
  • Rats

ASJC Scopus subject areas

  • Physiology

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