Construction Of Type 2 Diabetic Rat Models And The Preliminary Treatment Effectiveness Of Adipsin Mediated By Recombinant Adenovirus In The T2DM Rat Models

Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease characterized by hyperglycemia, insulin resistance and insulinopenia resulting from P cell failure and decreases in β cell mass. Obesity, adipose inflammation, and malfunction of β cells are tightly associated with one another, but the molecular link remains to be established. Adipsin was the first adipokine described and it is one of the major proteins of adipose cells but paradoxically declines in many animal models of obesity and diabetes. Animals genetically lacking adipsin have glucose intolerance due to insulinopenia but replenishment of adipsin to diabetic mice treated hyperglycemia by boosting insulin secretion. All these findings indicate that the adipsin pathway connects adipocyte function to β cell physiology, and manipulation of this molecular switch may serve as a therapy in T2DM.To evaluated whether the treatment with adipsin could prevent and serve as a therapy in the metabolic abnormalities associated with diabetes and obesity.First we establish a type 2 diabetes mellitus Sprague Dawley (SD) rats model, by using the high fatty diet plus low dose STZ injection and the type 2 diabetes SD rats model have the character with hyperglycemia and insulin resistance which is similar to the Zucker Diabetic Fatty (ZDF) rats. Then we construct a recombinant adenovirus carrying the gene of adipsin (Ad-adipsin) that expressing the protein of adipsin in the HEK293 cells and both the ZDF rats and T2DM SD rats were injected intravenously with Ad-lacZ or Ad-adipsin.Experimental result show that both the ZDF rats and T2DM SD rats were injected intravenously with ad-adipsin had a significantly overexpression of adipsin and reduced serum resistin, fasting blood glucose (FPG) levels, fasting insulin value(FINS), total serum cholest(TC),triglyceride(TG),and low density lipoprotein(LDL) on 7th day after treatment (P<0.05). In addition, glucose tolerance and insulin sensitivity were markedly increased (P<0.05). These results indicate that treatment with Ad-adipsin improves glucose and fat metabolism in type 2 diabetic rats.