title: Inhibitory effects of leptin on pancreatic alpha-cell function.
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.
  
  
  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.
authors.affiliation: Instituto de Bioingeniería, Universidad Miguel Hernandez, Elche, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Tudurí
authors.forename: Laura
authors.initials: L
authors.lastname: Marroquí
authors.forename: Sergi
authors.initials: S
authors.lastname: Soriano
authors.forename: Ana B
authors.initials: AB
authors.lastname: Ropero
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Batista
authors.forename: Sandra
authors.initials: S
authors.lastname: Piquer
authors.forename: Miguel A
authors.initials: MA
authors.lastname: López-Boado
authors.forename: Everardo M
authors.initials: EM
authors.lastname: Carneiro
authors.forename: Ramón
authors.initials: R
authors.lastname: Gomis
authors.forename: Angel
authors.initials: A
authors.lastname: Nadal
authors.forename: Ivan
authors.initials: I
authors.lastname: Quesada
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D005089:Exocytosis; D005934:Glucagon / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D054411:Receptors, Leptin / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D012313:RNA; D005934:Glucagon; D002118:Calcium