Effects of Vaspin on Pancreatic Beta Cell Function in Type 2 Diabetic Rats by AMPK/mTOR Autophagy Signaling Pathway

To investigate the mechanism of Vaspin in improving the pancreatic beta cell function in type 2 diabetic (T2DM) rats.

The diabetic rat model was established by feeding high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin. T2DM rats were randomly divided into T2DM group(n=10) and Vaspin group(n=10), with the same age SD rats fed with normal chow as normal control group (n=10). Before modeling, before Vaspin intervention, at 4 weeks and 8 weeks Vaspin intervention, the level of body weight and fasting blood-glucose(FBG) of rats were recorded. At 8 weeks of Vaspin intervention, fasting insulin (FINS), glucose tolerance and insulin sensitivity, pancreatic β-cell function and autophagy-related protein expression levels were measured in three groups of rats, and histopathological morphology of the pancreas was observed.

Before Vaspin intervention, at the 4 weeks and 8 weeks Vaspin intervention, compared with the normal control group, the level of body weight decreased and FBG increased in T2DM group and Vaspin group(all P < 0.05). At 8 weeks Vaspin intervention, compared with T2DM group, the level of body weight increased and FBG decreased in Vaspin group (all P < 0.05). Histopathology showed that the pancreatic tissue was normal, islet cells were arranged evenly, neatly and regularly in normal control group. In T2DM group, the islet structure was obviously destroyed, and the cells were unevenly distributed and irregularly shaped. Compared with T2DM group, the structural damage and morphological damage of islet cells in Vaspin group were significantly reduced. At the 8 weeks intervention, compared with the normal control group, the level of FINS decreased, while the area under the blood glucose curve of intraperitoneal glucose tolerance test(IPGTT) and intraperitoneal insulin tolerance test(IPITT) increased in T2DM group and Vaspin group(all P < 0.05). Compared with T2DM group, the level of FINS increased, while the area under blood glucose curve of IPGTT and IPITT decreased in Vaspin group(all P < 0.05). At the 8 weeks intervention, the high glucose clamp test showed that the glucose infusion rate, the level of insulin secretion in the first phase and the second phase in Vaspin group were lower than those in the normal control group, but all indexes in Vaspin group were higher than those in T2DM group (all P < 0.05). At the 8 weeks intervention, immunohistochemical and Western blot results showed that compared with the normal control group, the level of insulin expression and the ratio of p-mTOR/mTOR in pancreatic tissue of rats in T2DM group decreased, while the protein levels of P62, microtubule associated protein 1 light chain 3 (LC3), p-AMPK/AMPK ratio and LC3 Ⅱ/LC3 Ⅰ ratio increased. Compared with T2DM group, the levels of insulin, LC3 protein, p-AMPK/AMPK ratio and LC3 Ⅱ/LC3 Ⅰ ratio in pancreatic tissue of rats in Vaspin group increased, while p-mTOR/mTOR ratio and P62 protein expression decreased (all P < 0.05).

Vaspin can enhance the autophagy of pancreatic beta cells, improve pancreatic beta cells function by AMPK/mTOR signaling pathway in the type 2 diabetic rats.