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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 and Valmore Bermudez   Pages 1 - 17 ( 17 )

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 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, Leptinresistance, Diabetes, Obesity, Hyperleptinaemia, Insulinresistance, Central nervous system

Affiliation:

Endocrine and Metabolic Diseases Research Center. School of Medicine. The University of Zulia. Maracaibo, Endocrine and Metabolic Diseases Research Center. School of Medicine. The University of Zulia. Maracaibo, Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Endocrine and Metabolic Diseases Research Center. School of Medicine. The University of Zulia. Maracaibo, Endocrine and Metabolic Diseases Research Center. School of Medicine. The University of Zulia. Maracaibo, Endocrine and Metabolic Diseases Research Center. School of Medicine. The University of Zulia. Maracaibo, Endocrine and Metabolic Diseases Research Center. School of Medicine. The University of Zulia. Maracaibo, Universidad Católica de Cuenca. Provincia Azuay, Universidad Simón Bolívar, Facultad de Ciencias de la Salud, Barranquilla, Universidad Simón Bolívar, Facultad de Ciencias de la Salud, Barranquilla, Escuela de Nutrición y Dietética. Facultad de Medicina. Universidad Andrés Bello, Sede Concepción, Escuela de Nutrición y Dietética. Facultad de Medicina. Universidad Andrés Bello, Sede Concepción, Consorci Sanitari del Garraf. Hospital Sant Antoni Abat. Servicio de Nefrología. Barcelona, Universidad Simón Bolívar, Facultad de Ciencias de la Salud, Barranquilla



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