Reduced Insulin Secretion in Protein Malnourished Mice Is Associated with Multiple Changes in the beta-Cell Stimulus-Secretion Coupling
Contribuinte(s) |
Universidade Estadual Paulista (UNESP) |
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Data(s) |
20/05/2014
20/05/2014
01/08/2010
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Resumo |
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Processo FAPESP: 08/53811-8 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) |
Formato |
3543-3554 |
Identificador |
http://dx.doi.org/10.1210/en.2010-0008 Endocrinology. Chevy Chase: Endocrine Soc, v. 151, n. 8, p. 3543-3554, 2010. 0013-7227 http://hdl.handle.net/11449/42581 10.1210/en.2010-0008 WOS:000280171100009 WOS000280171100009.pdf |
Idioma(s) |
eng |
Publicador |
Endocrine Soc |
Relação |
Endocrinology |
Direitos |
closedAccess |
Tipo |
info:eu-repo/semantics/article |