Is "Leptin Resistance" Another Key Resistance to Manage Type 2 Diabetes?
Curr Diabetes Rev
; 16(7): 733-749, 2020.
Article
em En
| MEDLINE
| ID: mdl-31886750
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leptina
/
Diabetes Mellitus Tipo 2
/
Obesidade
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Diabetes Rev
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Venezuela
País de publicação:
Emirados Árabes Unidos