Impaired muscarinic type 3 (M3) receptor/PKC and PKA pathways in islets from MSG-obese rats
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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.
KeywordsInsulin secretion Monosodium glutamate Obesity M3 PKC PKA
This study was supported by grants from Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
Conflict of interest
The authors have no conflict of interest.
- 10.Balbo SL, Bonfleur ML, Carneiro EM, Amaral ME, Filiputti E, Mathias PC (2002) Parasympathetic activity changes insulin response to glucose and neurotransmitters. Diabetes Metab 28(6 Pt 2):13–17 discussion 13S108-112Google Scholar
- 14.Scomparin DX, Gomes RM, Grassiolli S, Rinaldi W, Martins AG, de Oliveira JC, Gravena C, de Freitas Mathias PC (2009) Autonomic activity and glycemic homeostasis are maintained by precocious and low intensity training exercises in MSG-programmed obese mice. Endocrine 36(3):510–517PubMedCrossRefGoogle Scholar
- 15.Andreazzi AE, Scomparin DX, Mesquita FP, Balbo SL, Gravena C, De Oliveira JC, Rinaldi W, Garcia RM, Grassiolli S, Mathias PC (2009) Swimming exercise at weaning improves glycemic control and inhibits the onset of monosodium l-glutamate-obesity in mice. J Endocrinol 201(3):351–359PubMedCrossRefGoogle Scholar
- 17.Ribeiro RA, Vanzela EC, Oliveira CA, Bonfleur ML, Boschero AC, Carneiro EM (2010) Taurine supplementation: involvement of cholinergic/phospholipase C and protein kinase A pathways in potentiation of insulin secretion and Ca2+ handling in mouse pancreatic islets. Br J Nutr 104(8):1148–1155PubMedCrossRefGoogle Scholar
- 19.Bergmeyer HU, Bernt E (1974) Determination of glucose with glucose oxidase and peroxidase. In: Bergeyer HU (ed) Methods of enzymatic analysis. Verlag Chemie, Weinhein, pp 1105–1212Google Scholar
- 20.Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T, Muggeo M (2000) Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 23(1):57–63PubMedCrossRefGoogle Scholar
- 32.Dolz M, Bailbe D, Giroix MH, Calderari S, Gangnerau MN, Serradas P, Rickenbach K, Irminger JC, Portha B (2005) Restitution of defective glucose-stimulated insulin secretion in diabetic GK rat by acetylcholine uncovers paradoxical stimulatory effect of beta-cell muscarinic receptor activation on cAMP production. Diabetes 54(11):3229–3237PubMedCrossRefGoogle Scholar