Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/80660
Type: Artigo de periódico
Title: Inhibitory Effects of Leptin on Pancreatic alpha-Cell Function
Author: Tuduri, E
Marroqui, L
Soriano, S
Ropero, AB
Batista, TM
Piquer, S
Lopez-Boado, MA
Carneiro, EM
Gomis, R
Nadal, A
Quesada, I
Abstract: OBJECTIVE-Leptin released from adipocytes plays a key role in the control of food intake, energy balance, and glucose homeostasis. In addition to its central action, leptin directly affects pancreatic beta-cells, inhibiting insulin secretion, and, thus, modulating glucose homeostasis. However, despite the importance of glucagon secretion in glucose homeostasis, the role of leptin in a-cell function has not been studied in detail. In the present study, we have investigated this functional interaction. RESEARCH DESIGN AND METHODS-The presence of leptin receptors (ObR) was demonstrated by RT-PCR analysis, Western blot, and immunocytochemistry. Electrical activity was analyzed by patch-clamp and Ca(2+) signals by confocal microscopy. Exocytosis and glucagon secretion were assessed using fluorescence methods and radioimmunoassay, respectively. RESULTS-The expression of several ObR isoforms (a-e) was detected in glucagon-secreting alpha TC1-9 cells. ObRb, the main isoform involved in leptin signaling, was identified at the protein level in alpha TC1-9 cells as well as in mouse and human alpha-cells. The application of leptin (6.25 nmol/l) hyperpolarized the alpha-cell membrane potential, suppressing the electrical activity induced by 0.5 mmol/l glucose. Additionally, leptin inhibited Ca(2+) signaling in alpha TC1-9 cells and in mouse and human alpha-cells within intact islets. A similar result occurred with 0.625 nmol/l leptin. These effects were accompanied by a decrease in glucagon secretion from mouse islets and were counteracted by the phosphatidylinositol 3-kinase inhibitor, wortmannin, suggesting the involvement of this pathway in leptin action. CONCLUSIONS-These results demonstrate that leptin inhibits alpha-cell function, and, thus, these cells are involved in the adipo-insular communication. Diabetes 58:1616-1624, 2009
Country: EUA
Editor: Amer Diabetes Assoc
Rights: fechado
Identifier DOI: 10.2337/db08-1787
Date Issue: 2009
Appears in Collections:Unicamp - Artigos e Outros Documentos

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