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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Reduced Insulin Secretion in Protein Malnourished Mice Is Associated with Multiple Changes in the beta-Cell Stimulus-Secretion Coupling

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Autor(es):
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Soriano, Sergi [1, 2] ; Gonzalez, Alejandro [1, 2] ; Marroqui, Laura [1, 2] ; Tuduri, Eva [1, 2] ; Vieira, Elaine [1, 2] ; Amaral, Andressa G. [3, 4] ; Batista, Thiago M. [3, 4] ; Rafacho, Alex [4, 5] ; Boschero, Antonio C. [3, 4] ; Nadal, Angel [1, 2] ; Carneiro, Everardo M. [3, 4] ; Quesada, Ivan [1, 2]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Univ Miguel Hernandez, Inst Bioingn, Elche 03202 - Spain
[2] Univ Miguel Hernandez, CIBER Diabet Enfermedades Metab Asociadas CIBERDE, Elche 03202 - Spain
[3] Univ Estadual Campinas, Dept Anat Biol Celular Fisiol Biofis, Inst Biol, BR-13083970 Campinas, SP - Brazil
[4] Inst Nacl Ciencia Tecnol Obesidade & Diabet, Sao Paulo - Brazil
[5] Univ Estadual Paulista, Dept Educacao Fis, Fac Ciencias, BR-17033360 Sao Paulo - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Endocrinology; v. 151, n. 8, p. 3543-3554, AUG 2010.
Citações Web of Science: 23
Resumo

The mechanism by which protein malnutrition impairs glucose-stimulated insulin secretion in the pancreatic beta-cell is not completely known but may be related to alterations in the signaling events involved in insulin release. Here, we aimed to study the stimulus-secretion coupling of beta-cells from mice fed with low-protein (LP) diet or normal-protein (NP) diet for 8 wk after weaning. Patch-clamp measurements in isolated cells showed that beta-cells from LP mice had a resting membrane potential that was more hyperpolarized than controls. Additionally, depolarization and generation of action potentials in response to stimulatory glucose concentrations were also impaired in beta-cells of LP mice. All these alterations in the LP group were most likely attributed to higher ATP-dependent K(+) (K(ATP)) channel activity in resting conditions and lower efficiency of glucose to induce the closure of these channels. Moreover, a Western blot analysis revealed higher protein levels of the sulphonylurea receptor of the K(ATP) channel in islets of LP mice. Because beta-cell Ca(2+) signals depend on electrical activity, intracellular Ca(2+) oscillations were measured by fluorescence microscopy in intact islets, indicating a lower response to glucose in the LP group. Finally, cell-to-cell synchrony of Ca(2+) signals was analyzed by confocal microscopy. Islets from LP mice exhibited a decreased level of coupling among beta-cells, which was probably due to the low expression levels of connexin 36. Therefore, low-protein diet leads to several alterations in the stimulus-secretion coupling of pancreatic beta-cells that might explain the diminished insulin secretion in response to glucose in this malnutrition state. (Endocrinology 151: 3543-3554, 2010) (AU)

Processo FAPESP: 08/53811-8 - Caracterização morfofuncional de ilhotas pancreáticas de camundongos submetidos à restrição protéica ou à dieta hiperlipídica e suplementados com taurina
Beneficiário:Everardo Magalhães Carneiro
Linha de fomento: Auxílio à Pesquisa - Regular