ADRENOCEPTOR ANTAGONISTS, BUT NOT GUANETHIDINE, REDUCE GLUCOPENIA-INDUCED GLUCAGON-SECRETION FROM PERFUSED RAT PANCREAS

This study was designed to investigate (1) whether norepinephrine is r eleased in response to glucopenia in vitro, thereby stimulating glucag on secretion and, (2) the modulating effects of norepinephrine on insu lin and glucagon secretion, using isolated perfused rat pancreas prepa rations. Simultaneous addition of the adrenergic receptor antagonists yohimbine, prazosin and propranolol, each at a concentration of 10(-5) mol/l, significantly potentiated glucose-stimulated insulin secretion (6.23 +/- 0.76 vs. 2.11 +/- 0.72 (control) nmol/min, P < 0.01), and s uppressed glucopenia-induced glucagon secretion (0.59 +/- 0.10 vs. 1.3 4 +/- 0.18 (control) ng/min, P < 0.05). Also, 10(-5) mol/l yohimbine a lone significantly potentiated glucose-stimulated insulin secretion (4 .86 +/- 0.50 nmol/min, P < 0.05). The norepinephrine release inhibitor , guanethidine, significantly inhibited tyramine-induced secretion of both norepinephrine (7.86 +/- 0.77 vs. 49.7 +/- 2.3 nmol/min, P < 0.01 ) and glucagon (0.31 +/- 0.08 vs. 1.21 +/- 0.15 ng/min, P < 0.01), but exerted no effects on glucopenia-induced secretion of either norepine phrine or glucagon. We conclude that these results further support the concept that the neurotransmitter norepinephrine is released in respo nse to glucopenia in vitro, and modulates insulin and glucagon secreti on. Our data do not, however, provide evidence indicating that glucope nia-induced glucagon secretion is mainly mediated by activation of sym pathetic nerve terminals around the alpha-cells in the isolated perfus ed rat pancreas.