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Type: Artigo de periódico
Title: Reduced Insulin Secretion in Protein Malnourished Mice Is Associated with Multiple Changes in the beta-Cell Stimulus-Secretion Coupling
Author: Soriano, S
Gonzalez, A
Marroqui, L
Tuduri, E
Vieira, E
Amaral, AG
Batista, TM
Rafacho, A
Boschero, AC
Nadal, A
Carneiro, EM
Quesada, I
Abstract: 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)
Country: EUA
Editor: Endocrine Soc
Citation: Endocrinology. Endocrine Soc, v. 151, n. 8, n. 3543, n. 3554, 2010.
Rights: embargo
Identifier DOI: 10.1210/en.2010-0008
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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