Central effects of beta-endorphins on glucose homeostasis in the conscious dog

Abstract

The effects of centrally administered beta-endorphins on glucose homeostasis in the conscious dog were studied. Intracerebroventricular administration of beta-endorphin (0.2 mg/h) caused a 70% increase in plasma glucose. The mechanism of the hyperglycemia was twofold: there was an early increase in glucose production and a late inhibition of glucose clearance. These changes are explained by marked increases in plasma epinephrine (30-fold) and norepinephrine (6-fold) that occurred during infusion of beta-endorphin. Central administration of beta-endorphin also resulted in increased levels of adrenocorticotropic hormone and cortisol. In addition there was an increase in plasma insulin but no increase in plasma glucagon. Intravenous administration of beta-endorphin did not alter glucose homeostasis. Intracerebroventricular administration of acetylated beta-endorphin did not perturb glucose kinetics or any of the hormones that changed during infusion of the unacetylated peptide. We conclude that beta-endorphin acts centrally to cause hyperglycemia by stimulating sympathetic outflow and the pituitary-adrenal axis. Acetylation of beta-endorphin abolishes the in vivo activity of the peptide.

Effects of intracerebroventricularly administered opioid peptide antagonists on tissue glycogen levels in rats after exercise

“…Hashiguchi et al administered intracerebroventricularly to demonstrate the effect of central opioids on glycogen levels in peripheral tissues as we did in our study [16]. Radosevich et al practiced on dogs to demonstrate icv and iv effects of β-endorphins on blood glucose level; they reported that central administration had increased blood glucose levels whereas peripheral application did not affect glucose homeostasis [20]. Various studies also report that these effects of endogenous opioid peptides can be antagonized with naloxone in experimental conditions [21].…”

F-DIO obesity-prone rat is insulin resistant before obesity onset

“…In addition to ␣-MSH, POMC also is a prohormone for ␤-endorphin, a hormone which increases intake of palatable diets (7). Central administration of ␤-endorphin also produces a strainand site-dependent elevation of blood glucose and possibly insulin levels (2,37). Thus, if elevated ARC POMC expression were associated with increased ␤-endorphin production and release, this might predispose nonobese F-DIO rats to develop abnormal glucose metabolism and to eat more and gain more weight when exposed to the high corn oil and sucrose content of the HE diet.…”

Activation of nucleus accumbens μ‐opioid receptors enhances the response to a glycaemic challenge

“…Previous studies have investigated the effects of i.c.v. infusion of the endogenous opioid β-endorphin [13], the synthetic μ-opioid receptor agonist morphine [3] or DAMGO [14] on blood glucose levels.…”

“…To investigate central opioid stimulation and glucose control, i.c.v. infusion of opioids has been used [2,13,14], thereby simultaneously affecting multiple brain areas. Because opioid receptors are expressed throughout the brain [15], it is unclear which brain areas are responsible for the changes seen in glycaemia upon i.c.v.…”