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

Abstract

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 b-cell of the endocrine pancreas is a critical target of leptin actions. Leptin receptors are present in the b-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, b-cell mass can be affected by leptin through changes in proliferation, apoptosis, or cell size. All these different functions in the b-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 b-cell population. Furthermore, it has been proposed that alterations in this level of regulation could contribute to the impairment of b-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 b-cell.

Metabolic risk factors in obesity and diabetes mellitus: implications in the pathogenesis and therapy

“…Leptin resistance occurs primarily due to increased circulating leptin levels and its mRNA expression in adipose tissue in obese subjects [37,38]. Leptin regulates pancreatic β-cell function as well as improves insulin sensitivity in the liver and skeletal muscle [39]. Leptin alongwith monocytes induces the rele ase of pro-inflammatory cytokines such as TNF-a or IL-6 as well as CCL2 and VEGF [40].…”

Związek hormonów pochodzących z tkanki tłuszczowej z cukrzycą ciążową (GDM)

“…Leptin can also directly affect pancreas function through inhibiting b-cell insulin secretion and several mechanisms engaged in this process have been proposed, including (i) reduction of proinsulin mRNA level in pancreatic b-cells under high glucose concentrations, (ii) suppression of glucose transport into b-cells, (iii) PI3K-dependent activation of PDE3B that leads to a reduction of cAMP level and, in turn, inhibition of protein kinase A (PKA) involved in the regulation of Ca 2+ channels and exocytosis, and (iv) inhibition of the phospholipase C (PLC)/protein kinase C (PKC) pathway [29].…”

Association of Leptin Receptor Gene Gln223Arg and lys109Arg Polymorphisms with Obesity and Overweight in an Iranian Young Population

“…LRb is the longest isoform of leptin receptor with a length of 1165 amino acids while its intracellular domain is composed of 304 amino acids. The LRb is expressed in the hypothalamus in high levels and its presence is essential for leptin signaling (11).…”