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 alpha-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 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. CONCLUSIONS:These results demonstrate that leptin inhibits alpha-cell function, and, thus, these cells are involved in the adipoinsular communication.
journal_name
Diabetesjournal_title
Diabetesauthors
Tudurí E,Marroquí L,Soriano S,Ropero AB,Batista TM,Piquer S,López-Boado MA,Carneiro EM,Gomis R,Nadal A,Quesada Idoi
10.2337/db08-1787subject
Has Abstractpub_date
2009-07-01 00:00:00pages
1616-24issue
7eissn
0012-1797issn
1939-327Xpii
db08-1787journal_volume
58pub_type
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