Inhibitory Effects of Leptin on Pancreatic α-Cell Function
Eva Tudurí 1 , 2 ,
Laura Marroquí 1 , 2 ,
Sergi Soriano 1 , 2 ,
Ana B. Ropero 1 , 2 ,
Thiago M. Batista 3 ,
Sandra Piquer 2 , 4 ,
Miguel A. López-Boado 5 ,
Everardo M. Carneiro 3 ,
Ramón Gomis 2 , 4 ,
Angel Nadal 1 , 2 and
Ivan Quesada 1 , 2
1 Instituto de Bioingeniería, Universidad Miguel Hernandez, Elche, Spain;
2 CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain;
3 Instituto Nacional de Pesquisa em Obesidade e Diabetes, Departmento de Anatomia, Biologia Celulare Fisiologia, Institute of
Biology, Unicamp, Campinas, Brazil;
4 Endocrinology and Diabetes Unit, Laboratory of Diabetes and Obesity, IDIBAPS-Fundació Clínic, Hospital Clínic, Barcelona,
Spain;
5 Institut de Malalties Digestives i Metabòliques, Hospital Clínic, Barcelona, Spain.
Corresponding author: Ivan Quesada, ivanq{at}umh.es .
E.T. and L.M. contributed equally to this work.
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 β-cells, inhibiting insulin secretion, and, thus, modulating
glucose homeostasis. However, despite the importance of glucagon secretion in glucose homeostasis, the role of leptin in α-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 αTC1-9 cells. ObRb, the main isoform involved
in leptin signaling, was identified at the protein level in αTC1-9 cells as well as in mouse and human α-cells. The application
of leptin (6.25 nmol/l) hyperpolarized the α-cell membrane potential, suppressing the electrical activity induced by 0.5 mmol/l
glucose. Additionally, leptin inhibited Ca 2+ signaling in αTC1-9 cells and in mouse and human α-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 α-cell function, and, thus, these cells are involved in the adipoinsular communication.
Footnotes
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
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Received December 23, 2008.
Accepted April 2, 2009.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
© 2009 by the American Diabetes Association....

Inhibitory Effects of Leptin on Pancreatic α-Cell Function

10.2337/db08-1787