Alteration of NPY in hypothalamus and its correlation with leptin and ghrelin during the development of T2DM in a rat model

OBJECTIVES: This study aimed to investigate the alteration of Neuropeptide Y (NPY) in the hypothalamus and its correlation with insulin, leptin and ghrelin during the development of a rat model of type 2 diabetes mellitus. METHODS: The type 2 diabetes mellitus model was developed in diet-induced obesity (DIO) rats followed by the intraperitoneal injection of low-dose streptozotocin (STZ, 25 mg/kg). At four time points during the development of type 2 diabetes mellitus in rats, the fasting serum insulin, leptin, and plasma ghrelin were measured and the hypothalamic neuropeptide Y (NPY) content and mRNA expression were detected in the rats, which were divided into 4 groups: normal control (NC), DIO(4W), DIO(8W), and T2DM; the mRNA expression of OB-Rb, and GSH-R1a in the hypothalamus were also assayed. RESULTS: During the development of the type 2 diabetes mellitus rat model, both the fasting serum levels of insulin and leptin (ng/ml) elevated significantly and the fasting plasma ghrelin concentration decreased the hypothalamic NPY (pg/mg) content significantly. NPY mRNA increased significantly in a time-dependent fashion while both the OB-Rb and the GHS-R1a mRNA of the hypothalamus decreased significantly. Hypothalamic NPY concentration was positively correlated with the changes in serum insulin and leptin and negatively correlated with plasma ghrelin. CONCLUSIONS: During the development of the type 2 diabetes mellitus rat model, the hypothalamic NPY content and NPY mRNA expression increased in a time-dependent manner, which was positively correlated with the changes of the serum insulin and leptin and negatively correlated with the plasma ghrelin.