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 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.