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Impaired muscarinic type 3 (M3) receptor/PKC and PKA pathways in islets from MSG-obese rats

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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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Universidade Federal do Rio de Janeiro (UFRJ), Campus UFRJ, Macaé, RJ, Brazil

    Rosane Aparecida Ribeiro

  2. Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, CEP 858119-110, Brazil

    Sandra Lucinei Balbo, Luiz Felipe Barella & Maria Lúcia Bonfleur

  3. Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil

    Letícia Prates Roma, Rafael Ludemann Camargo, Emerielle Cristine Vanzela, Everardo Magalhães Carneiro & Antonio Carlos Boschero

  4. Laboratório de Biologia Celular da Secreção, Universidade Estadual de Maringá (UEM), Maringá, PR, Brazil

    Paulo Cesar de Freitas Mathias

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  1. Rosane Aparecida Ribeiro
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Correspondence to Maria Lúcia Bonfleur.

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Ribeiro, R.A., Balbo, S.L., Roma, L.P. et al. Impaired muscarinic type 3 (M3) receptor/PKC and PKA pathways in islets from MSG-obese rats. Mol Biol Rep 40, 4521–4528 (2013). https://doi.org/10.1007/s11033-013-2546-y

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  • DOI: https://doi.org/10.1007/s11033-013-2546-y

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