methylnaltrexone and Hypoglycemia

In this study, we investigated the effects of recurrent hypoglycaemia on the adrenal catecholamine synthetic enzymes in a rat model of hypoglycaemia-associated autonomic failure (HAAF). We found that plasma adrenaline was significantly reduced by about 50% in response to recurrent hypoglycaemia versus single hypoglycaemia. However, tyrosine hydroxylase (TH) protein and phosphorylation at Ser31 and Ser40 were increased in HAAF; similarly, aromatic aminoacid decarboxylase protein was also increased indicating a likely increase in catecholamine synthesis in the adrenal gland. Opioid antagonists, naloxone and methylnaltrexone did not restore plasma adrenaline in HAAF; however, naloxone increased TH phosphorylation at Ser31 and Ser40.

Topics: Animals; Blood Glucose; Disease Models, Animal; Epinephrine; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Naloxone; Naltrexone; Narcotic Antagonists; Pure Autonomic Failure; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley; Serine; Tyrosine 3-Monooxygenase