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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Inhibitory Effects of Leptin on Pancreatic alpha-Cell Function

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Autor(es):
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Tuduri, Eva [1, 2] ; Marroqui, Laura [1, 2] ; Soriano, Sergi [2, 1] ; Ropero, Ana B. [1, 2] ; Batista, Thiago M. [3] ; Piquer, Sandra [1, 4] ; Lopez-Boado, Miguel A. [5] ; Carneiro, Everardo M. [3] ; Gomis, Ramon [1, 4] ; Nadal, Angel [1, 2] ; Quesada, Ivan [1, 2]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] CIBER Diabet & Enfermedades Metab Asociadas, Barcelona - Spain
[2] Univ Miguel Hernandez, Inst Bioingn, Elche - Spain
[3] Univ Estadual Campinas, Inst Biol, Dept Anat, Inst Nacl Pesquisas Obesidade & Diabet, Campinas, SP - Brazil
[4] Hosp Clin Barcelona, IDIBAPS Fundacio Clin, Lab Diabet & Obes, Endocrinol & Diabet Unit, Barcelona - Spain
[5] Hosp Clin Barcelona, Inst Malalties Digest & Metab, Barcelona - Spain
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Diabetes; v. 58, n. 7, p. 1616-1624, JUL 2009.
Citações Web of Science: 46
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 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 (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
Linha de fomento: Auxílio à Pesquisa - Regular