Chronic orexin-A (hypocretin-1) treatment of type 2 diabetic rats improves glucose control and beta-cell functions.
J Physiol Pharmacol
; 68(5): 669-681, 2017 Oct.
Article
en En
| MEDLINE
| ID: mdl-29375041
ABSTRACT
Orexin regulates food intake and energy expenditure. Here, we test the ability of orexin-A (OXA, hypocretin-1) at improving metabolic control in type 2 diabetic animals and elaborate potential mechanisms of action. Rats with experimentally induced type 2 diabetes by a combination of streptozotocin injection and high-fat diet feeding were chronically infused with OXA. In vitro experiments were conducted on isolated pancreatic islets, primary adipocytes and insulin secreting INS-1E cells. OXA improved glucose control, enhanced insulin sensitivity and attenuated pancreatic ß-cell loss in type 2 diabetic rats. Ex vivo, apoptotic death of pancreatic islets isolated from OXA-treated type 2 diabetic animals as well as the impairment of glucose-stimulated insulin secretion were attenuated, as compared to islets derived from vehicle-treated rats. OXA reduced plasma tumor necrosis factor-α (TNF-α) and non-esterified fatty acids (NEFA) levels in type 2 diabetic rats. OXA decreased palmitate- and TNF-α-induced apoptosis of INS-1E cells. OXA improves glucose control by enhancing insulin sensitivity and protecting ß-cells from apoptotic cell death in type 2 diabetic animals.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glucemia
/
Diabetes Mellitus Experimental
/
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
/
Orexinas
Límite:
Animals
Idioma:
En
Revista:
J Physiol Pharmacol
Asunto de la revista:
FARMACOLOGIA
/
FISIOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Polonia