title: Insulin oversecretion in MSG-obese rats is related to alterations in cholinergic muscarinic receptor subtypes in pancreatic islets.
abstract: OBJECTIVE
  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.
authors.affiliation: Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics, State University of Maringá - Maringá/PR, Brazil.
authors.forename: Rosiane A
authors.initials: RA
authors.lastname: Miranda
authors.forename: Aryane R
authors.initials: AR
authors.lastname: Agostinho
authors.forename: Isis H
authors.initials: IH
authors.lastname: Trevenzoli
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Barella
authors.forename: Claudinéia C S
authors.initials: CC
authors.lastname: Franco
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Trombini
authors.forename: Ananda
authors.initials: A
authors.lastname: Malta
authors.forename: Clarice
authors.initials: C
authors.lastname: Gravena
authors.forename: Rosana
authors.initials: R
authors.lastname: Torrezan
authors.forename: Paulo C F
authors.initials: PC
authors.lastname: Mathias
authors.forename: Júlio C
authors.initials: JC
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D043585:Receptor, Muscarinic M2 / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000378:metabolism; D043588:Receptor, Muscarinic M4 / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000737:chemistry / Q000378:metabolism*; D012970:Sodium Glutamate / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; D012970:Sodium Glutamate