Role of leptin in the pancreatic β-cell: effects and signaling pathways

Leptin plays an important role in the control of food intake, energy expenditure, metabolism, and body weight. This hormone also has a key function in the regulation of glucose homeostasis. Although leptin acts through central and peripheral mechanisms to modulate glucose metabolism, the pancreatic beta-cell of the endocrine pancreas is a critical target of leptin actions. Leptin receptors are present in the beta-cell, and their activation directly inhibits insulin secretion from these endocrine cells. The effects of leptin on insulin occur also in the long term, since this hormone inhibits insulin gene expression as well. Additionally, beta-cell mass can be affected by leptin through changes in proliferation, apoptosis, or cell size. All these different functions in the beta-cell are triggered by leptin as a result of the large diversity of signaling pathways that this hormone is able to activate in the endocrine pancreas. Therefore, leptin can participate in glucose homeostasis owing to different levels of modulation of the pancreatic beta-cell population. Furthermore, it has been proposed that alterations in this level of regulation could contribute to the impairment of beta-cell function in obesity states. In the present review, we will discuss all these issues with special emphasis on the effects and pathways of leptin signaling in the pancreatic beta-cell.