Effects of α₂- and β-adrenergic agonism on glucagon secretion from perfused pancreata of normal and streptozocin-induced diabetic rats

Insulin secretion is known to be inhibited by α₂-adrenergic agonism and stimulated by β-adrenergic agonism in both experimental animals and humans. In contrast, adrenergic regulation of glucagon secretion remains controversial. This study was designed to determine the effects of α₂- and β-adrenergic agonism on islet α cells, using isolated perfused pancreata of normal and streptozocin-induced diabetic (STZ-D) rats. The α₂-adrenoceptor agonist clonidine at a concentration of 10^-7 mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (1,286 ± 90 v 417 ± 53 ng/L, P < .01) and STZ-D rats (551 ± 86 v 130 ± 19 ng/L, P < .01). Also, the β-adrenoceptor agonist isoproterenol at a concentration of 10^-7 mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (751 ± 130 v 347 ± 41 ng/L, P < .05) and STZ-D rats (182 ± 22 v 92 ± 20 ng/L, P < .01). Furthermore, these α₂- and β-agonistic effects were almost completely inhibited in the presence of the α₂-adrenoceptor antagonist yohimbine and the β-agonistic effects were almost propranolol at a concentration of 10^-6 mol/L, respectively. Insulin secretion was markedly reduced in STZ-D rats. These results suggest that even in a severely diabetic state, not only β- but also α₂-adrenergic agonism stimulates glucagon secretion from rat pancreatic α cells.