Inhibitory Effects of Leptin on Pancreatic α-Cell Function

  1. Eva Tudurí1,2,
  2. Laura Marroquí1,2,
  3. Sergi Soriano1,2,
  4. Ana B. Ropero1,2,
  5. Thiago M. Batista3,
  6. Sandra Piquer2,4,
  7. Miguel A. López-Boado5,
  8. Everardo M. Carneiro3,
  9. Ramón Gomis2,4,
  10. Angel Nadal1,2 and
  11. Ivan Quesada1,2
  1. 1Instituto de Bioingeniería, Universidad Miguel Hernandez, Elche, Spain;
  2. 2CIBER de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain;
  3. 3Instituto Nacional de Pesquisa em Obesidade e Diabetes, Departmento de Anatomia, Biologia Celulare Fisiologia, Institute of Biology, Unicamp, Campinas, Brazil;
  4. 4Endocrinology and Diabetes Unit, Laboratory of Diabetes and Obesity, IDIBAPS-Fundació Clínic, Hospital Clínic, Barcelona, Spain;
  5. 5Institut de Malalties Digestives i Metabòliques, Hospital Clínic, Barcelona, Spain.
  1. Corresponding author: Ivan Quesada, ivanq{at}
  1. E.T. and L.M. contributed equally to this work.


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 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 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 Ca2+ 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.


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    • Received December 23, 2008.
    • Accepted April 2, 2009.
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