Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/52803
Type: Artigo de periódico
Title: Lower expression of PKA alpha impairs insulin secretion in islets isolated from low-density lipoprotein receptor (LDLR-/-) knockout mice
Author: Bonfleur, ML
Ribeiro, RA
Balbo, SL
Vanzela, EC
Carneiro, EM
de Oliveira, HCF
Boschero, AC
Abstract: Hypercholesterolemic low-density lipoprotein receptor knockout mice (LDLR-/-) show normal whole-body insulin sensitivity, but impaired glucose tolerance due to a reduced insulin secretion in response to glucose. Here, we investigate the possible mechanisms involved in such a defect in isolated LDLR-/- mice islets. Low-fat chow-fed female and male mice aged 20 weeks, LDLR-/- mice, and wild-type (WT) mice were used in this study. Static insulin secretion, cytoplasmatic Ca2+ analysis, and protein expression were measured in islets isolated from LDLR-/- and WT mice. At basal (2.8 mmol/L) and stimulatory (11.1 mmol/L) glucose concentrations, the insulin secretion rates induced by depolarizing agents such as KCl, L-arginine, and tolbutamide were significantly reduced in LDLR-/- when compared with control (WT) islets. In addition, KCl-induced Ca2+ influx at 2.8 mmol/L glucose was lower in LDLR-/- islets, suggesting a defect downstream of the substrate metabolism step of the insulin secretion pathway. Insulin secretion induced by the protein kinase A (PKA) activators forskolin and 3-isobutyl-1-methyl-xanthine, in the presence of 11.1 mmol/L glucose, was lower in LDLR-/- islets and was normalized in the presence of the protein kinase C pathway activators carbachol and phorbol 12-myristate 13-acetate. Western blotting analysis showed that phospholipase C beta(2) expression was increased and PKA alpha was decreased in LDLR-/- compared with WT islets. Results indicate that the lower insulin secretion observed in islets from LDLR-/- mice at postprandial levels of glucose can be explained, at least in part, by the reduced expression of PKA alpha in these islets. (C) 2011 Elsevier Inc. All rights reserved.
Country: EUA
Editor: W B Saunders Co-elsevier Inc
Rights: fechado
Identifier DOI: 10.1016/j.metabol.2010.12.010
Date Issue: 2011
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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