| Texto completo | |
| Autor(es): Mostrar menos - |
Tuduri, Eva
;
Marroqui, Laura
;
Soriano, Sergi
;
Ropero, Ana B.
;
Batista, Thiago M.
;
Piquer, Sandra
;
Lopez-Boado, Miguel A.
;
Carneiro, Everardo M.
;
Gomis, Ramon
;
Nadal, Angel
;
Quesada, Ivan
Número total de Autores: 11
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Diabetes; v. 58, n. 7, p. 9-pg., 2009-07-01. |
| Resumo | |
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 Ca2+ 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 Ca2+ 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 (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 |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |