Hypoinsulinemic and Hyperglycemic Effects of β-Endorphin in Rabbits

Summary

The present study was designed to investigate the in vivo effects of β-endorphin on plasma levels of glucagon, insulin and glucose in rabbits, and to elucidate some of the mechanisms involved. β-Endorphin (50 μg) injected intravenously into fasted rabbits, decreased plasma levels of insulin (-4.5±1.3 μU/ml, P < 0.05) and increased plasma levels of glucose (+2.7±0.4 mmol/l, P < 0.05). Similar hypoinsulinemic and hyperglycemic effects were observed for 25 and 2.5 μg β-endorphin in fasted and 50 and 0.5 μg β-endorphin in fed rabbits. β-Endorphin produced slight and transient increases in plasma levels of glucagon at the highest dose in fed rabbits, only (+80±9 pg/ml, P < 0.05). The β-endorphin-induced hypoinsulinemia was not inhibited by phentolamine, yohimbine, propranolol or atropine, which is in consistence with a direct inhibitory effect of β-endorphin on the β-cell in rabbits. The β-endorphin-induced hyperglycemia was reduced by naloxone (+0.8±0.1 mmol/l) but not by N-methyl-naloxone (ORG 10908) a peripheral opiate receptor blocking drug (+2.2±0.2 mmol/l), suggesting a central nervous action on opiate receptors. This central action of β-endorphin was probably not mediated by catecholamine release or other stimulation of adrenergic or muscarinic receptors, since the β-endorphin-induced hyperglycemia was not inhibited by phentolamine, yohimbine, propranolol or atropine. These results suggest that the β-endorphin-induced hyperglycemia was caused, at least in part, by a peripheral inhibition of insulin release and a central stimulation on glucoregulation.

Key-Words

β-Endorphin - Naloxone - N-methyl-Naloxone (ORG 10908) - Phentolamine - Yohimbine - Propranolol - Atropine - Glucagon - Insulin - Glucose - Rabbits