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

Abstract

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) M₁-M₄ 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 M₂mAChR-selective antagonist increased secretion. Moreover, the insulinostatic effect of an M₃mAChR-selective antagonist was significantly higher in the MSG-treated group. M₁mAChR and M₃mAChR expression was increased in the MSG-obese group by 55% and 73%, respectively. In contrast, M₂mAChR expression decreased by 25% in the MSG group, whereas M₄mAChR expression was unchanged. Conclusions: Functional changes in and altered content of the mAChR (M₁-M₄) 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.

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

“…High protein expression of M 3 AChR was recently registered (Miranda et al 2014) as was high vagus nerve activity in the MSG-obesity model reported by our group (Balbo et al 2002, Miranda et al 2014. Adrenalectomy as observed in this study was able to reduce M 3 AChR levels in the islets and inhibit electrical vagal activity.…”

“…The cholinergic response was decreased in pancreatic islets isolated from MSGobese rats compared with lean rats; however, the protein expression of M 3 AChR was increased (Miranda et al 2014). In the animals treated with dexamethasone, an enhancement of M 3 AChR in pancreatic islets was found (Angelini et al 2010).…”

“…Islets from obese rats presented a higher response to glucose than those from lean rats (Miranda et al 2014). Vagotomy and adrenalectomy or both improved GIIS in isolated islets.…”

“…Pancreatic islets from MSG-obese rats incubated with carbachol, a cholinergic muscarinic agonist, showed lower insulin secretion than those from lean rats, demonstrating a weak cholinergic response (Balbo et al 2002); however, M 3 AChR was shown to be highly expressed in the pancreatic islets from MSG-obese rats (Miranda et al 2014).…”

Características nociceptivas e histomorfométricas de nervos medianos de ratos com obesidade induzida pelo glutamato monossódico

“…21 Davidson et al, 9 avaliando a progressão da neuropatia periférica em ratos obesos (com dieta rica em gordura) e diabéticos, observaram que ambos foram resistentes à insulina, sendo que desenvolveram déficits nervosos sensitivos, porém, apenas os diabéticos apresentaram déficits motores. Desta forma, buscou-se no presente estudo avaliar se animais pré-diabéticos, obesos, apresentariam diferenças funcionais e morfométricas em nervos medianos, quando comparados com animais eutróficos.…”