Is “Leptin Resistance” Another Key Resistance to Manage Type 2 Diabetes?

Author(s): Juan Salazar*, Mervin Chávez-Castillo, Joselyn Rojas, Angel Ortega, Manuel Nava, José Pérez, Milagros Rojas, Cristobal Espinoza, Maricarmen Chacin, Yaneth Herazo, Lissé Angarita, Diana Marcela Rojas, Luis D’Marco, Valmore Bermudez

Journal Name: Current Diabetes Reviews

Volume 16 , Issue 7 , 2020

Become EABM
Become Reviewer

Abstract:

Although novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus.

Keywords: Leptin, leptin resistance, diabetes, obesity, hyperleptinemia, insulin resistance, adipokines.

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 7
Year: 2020
Page: [733 - 749]
Pages: 17
DOI: 10.2174/1573399816666191230111838
Price: $65

Article Metrics

PDF: 13