title: Impaired muscarinic type 3 (M3) receptor/PKC and PKA pathways in islets from MSG-obese rats.
abstract: Monosodium glutamate-obese rats are glucose intolerant and insulin resistant. Their pancreatic islets secrete more insulin at increasing glucose concentrations, despite the possible imbalance in the autonomic nervous system of these rats. Here, we investigate the involvement of the cholinergic/protein kinase (PK)-C and PKA pathways in MSG β-cell function. Male newborn Wistar rats received a subcutaneous injection of MSG (4 g/kg body weight (BW)) or hyperosmotic saline solution during the first 5 days of life. At 90 days of life, plasma parameters, islet static insulin secretion and protein expression were analyzed. Monosodium glutamate rats presented lower body weight and decreased nasoanal length, but had higher body fat depots, glucose intolerance, hyperinsulinemia and hypertrigliceridemia. Their pancreatic islets secreted more insulin in the presence of increasing glucose concentrations with no modifications in the islet-protein content of the glucose-sensing proteins: the glucose transporter (GLUT)-2 and glycokinase. However, MSG islets presented a lower secretory capacity at 40 mM K(+) (P < 0.05). The MSG group also released less insulin in response to 100 μM carbachol, 10 μM forskolin and 1 mM 3-isobutyl-1-methyl-xantine (P < 0.05, P < 0.0001 and P < 0.01). These effects may be associated with a the decrease of 46 % in the acetylcholine muscarinic type 3 (M3) receptor, and a reduction of 64 % in PKCα and 36 % in PKAα protein expressions in MSG islets. Our data suggest that MSG islets, whilst showing a compensatory increase in glucose-induced insulin release, demonstrate decreased islet M3/PKC and adenylate cyclase/PKA activation, possibly predisposing these prediabetic rodents to the early development of β-cell dysfunction.
authors: Universidade Federal do Rio de Janeiro (UFRJ), Campus UFRJ, Macaé, RJ, Brazil.
authors: Rosane Aparecida
authors: RA
authors: Ribeiro
authors: Sandra Lucinei
authors: SL
authors: Balbo
authors: Letícia Prates
authors: LP
authors: Roma
authors: Rafael Ludemann
authors: RL
authors: Camargo
authors: Luiz Felipe
authors: LF
authors: Barella
authors: Emerielle Cristine
authors: EC
authors: Vanzela
authors: Paulo Cesar
authors: PC
authors: de Freitas Mathias
authors: Everardo Magalhães
authors: EM
authors: Carneiro
authors: Antonio Carlos
authors: AC
authors: Boschero
authors: Maria Lúcia
authors: ML
authors: Bonfleur
mesh_terms: D000818:Animals; D001786:Blood Glucose; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004195:Disease Models, Animal; D000081410:Germinal Center Kinases; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D015398:Signal Transduction; D012970:Sodium Glutamate / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001786:Blood Glucose; D000081410:Germinal Center Kinases; D051273:Glucose Transporter Type 2; D007328:Insulin; D043587:Receptor, Muscarinic M3; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D005947:Glucose; D012970:Sodium Glutamate
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