Adrenoceptor antagonists, but not guanethidine, reduce glucopenia-induced glucagon secretion from perfused rat...

This study was designed to investigate (1) whether norepinephrine is released in response to glucopenia in vitro, thereby stimulating glucagon secretion and, (2) the modulating effects of norepinephrine on insulin and glucagon secretion, using isolated perfused rat pancreas preparations. 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 suppressed glucopenia-induced glucagon secretion (0.59 +/- 0.10 vs. 1.34 + 0.18 (control) ng/min, P < 0.05). Also, 10-(5) mol/l yohimbine alone 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 norepinephrine or glucagon. We conclude that these results further support the concept that the neurotransmitter norepinephrine is released in response to glucopenia in vitro, and modulates insulin and glucagon secretion. Our data do not, however, provide evidence indicating that glucopenia-induced glucagon secretion is mainly mediated by activation of sympathetic nerve terminals around the alpha-cells in the isolated perfused rat pancreas.