Inhibitory effects of leptin on pancreatic alpha-cell function.
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.
Tudurí
Eva
E
Instituto de Bioingeniería, Universidad Miguel Hernandez, Elche, Spain.
Marroquí
Laura
L
Soriano
Sergi
S
Ropero
Ana B
AB
Batista
Thiago M
TM
Piquer
Sandra
S
López-Boado
Miguel A
MA
Carneiro
Everardo M
EM
Gomis
Ramón
R
Nadal
Angel
A
Quesada
Ivan
I
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
D020738:Leptin; D054411:Receptors, Leptin; D012313:RNA; D005934:Glucagon; D002118:Calcium