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- Title
Inhibitory effects of leptin on pancreatic alpha-cell function.
- Authors
Tudurí E; Marroquí L; Soriano S; Ropero AB; Batista TM; Piquer S; López-Boado MA; Carneiro EM; Gomis R; Nadal A; Quesada I; Tudurí, Eva; Marroquí, Laura; Soriano, Sergi; Ropero, Ana B; Batista, Thiago M; Piquer, Sandra; López-Boado, Miguel A; Carneiro, Everardo M; Gomis, Ramón
- Abstract
<bold>Objective: </bold>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 alpha-cell function has not been studied in detail. In the present study, we have investigated this functional interaction.<bold>Research Design and Methods: </bold>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.<bold>Results: </bold>The expression of several ObR isoforms (a-e) was detected in glucagon-secreting alphaTC1-9 cells. ObRb, the main isoform involved in leptin signaling, was identified at the protein level in alphaTC1-9 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 alphaTC1-9 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.<bold>Conclusions: </bold>These results demonstrate that leptin inhibits alpha-cell function, and, thus, these cells are involved in the adipoinsular communication.
- Publication
Diabetes, 2009, Vol 58, Issue 7, p1616
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db08-1787