HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats.
Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus-pituitary-adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodium l-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX-VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3 muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX-VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity.
Department of BiotechnologyGenetics and Cell Biology, State University of Maringá, Maringá, Brazil Carlos Chagas Filho Biophysics InstituteFederal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Rosiane A
RA
Miranda
Department of Physiological SciencesState University of Maringá, Maringá, Brazil.
Rosana
R
Torrezan
Institute of Health SciencesFederal University of Mato Grosso, Sinop, Brazil.
Júlio C
JC
de Oliveira
Molecular Signalling SectionLaboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Luiz F
LF
Barella
Department of BiotechnologyGenetics and Cell Biology, State University of Maringá, Maringá, Brazil.
Claudinéia C
CC
da Silva Franco
Department of Physiological SciencesRoberto Alcântara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Patrícia C
PC
Lisboa
Department of Physiological SciencesRoberto Alcântara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Egberto G
EG
Moura
Department of BiotechnologyGenetics and Cell Biology, State University of Maringá, Maringá, Brazil pmathias@uem.br.
Paulo C F
PC
Mathias
D000818:Animals; D005947:Glucose / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012970:Sodium Glutamate; D014630:Vagus Nerve / Q000378:metabolism / Q000503:physiopathology*
D007328:Insulin; D005947:Glucose; D012970:Sodium Glutamate
HPA axis; M3 muscarinic receptor; MSG rats; PNS; insulin secretion