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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.

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