Insulin Oversecretion in MSG-Obese Rats is Related to Alterations in Cholinergic Muscarinic Receptor Subtypes in Pancreatic Islets

Background/Aims: Impaired pancreatic beta cell function and insulin secretion/action are a link between obesity and type 2 diabetes, which are worldwide public health burdens. We aimed to characterize the muscarinic acetylcholine receptor (mAChR) M-1-M-4 subtypes in isolated pancreatic islets from pre-diabetic obese rats that had been treated neonatally with monosodium L-glutamate (MSG). Methods: At 90 days of age, both the MSG and the control groups underwent biometric and biochemical evaluation. Anti-muscarinic drugs were used to study mAChR function either in vivo or in vitro. Results: The results demonstrated that atropine treatment reduced insulin secretion in the MSG-treated and control groups, whereas treatment with an M(2)mAChR-selective antagonist increased secretion. Moreover, the insulinostatic effect of an M(3)mAChR-selective antagonist was significantly higher in the MSG-treated group. M(1)mAChR and M(3)mAChR expression was increased in the MSG-obese group by 55% and 73%, respectively. In contrast, M(2)mAChR expression decreased by 25% in the MSG group, whereas M4mAChR expression was unchanged. Conclusions: Functional changes in and altered content of the mAChR (M-1-M-4) subtypes are pivotal to the demand for high pancreatic beta cell insulin secretion in MSG-obese rats, which is directly associated with vagal hyperactivity and peripheral insulin resistance. Copyright (C) 2014 S.Karger AG, Basel