Inhibitory effects of leptin on the 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 Quesada (ivanq{at},2
  1. 1Instituto de Bioingeniería, Universidad Miguel Hernandez, Elche, Spain
  2. 2CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain
  3. 3Instituto Nacional de Pesquisa em Obesidade e Diabetes, Department of Physiology and Biophysics, Institute of Biology, Unicamp, Campinas SP, 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


    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 the 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 nM) hyperpolarized the α-cell membrane potential, suppressing the electrical activity induced by 0.5 mM 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 nM leptin. These effects were accompanied by a decrease in glucagon secretion from mouse islets and counteracted by the PI3-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.


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