The Efficacy And Mechanism Of Action Of TZKP Against Type 2Diabetic Mellitus

ObjectiveType 2 diabetes(T2DM)is a kind of typical metabolic disease characterized by hyperglycemia and lipid metabolism disorders,can carries a 2-6-fold increased risk of cardiovascular disease and death.TZKP is a clinical prescription for the treatment of diabetes mellitus.This study explored the efficacy and mechanism of TZKP on type 2 diabetes mellitus by establishing T2DM models of various types of animals.MethodsIntramuscular injection of streptozotocin and high-fat diet were used to establish a T2DM model of NIH mice.Serum was used to detect glucose and lipid metabolism-related indicators,and the pharmacological effects of TZKP on T2DM.High-fat diet-induced obesity type 2 diabetic rats(ZDF)established a T2DM model.Serum and liver were used to detect glucose and lipid metabolism indicators AMPK/AKT/GS and CYP7A1/LCAT/LXRa pathway,and to explore TZKP-mediated glucose and lipid Mechanism of metabolism.Establish a golden hamster T2DM model by intramuscular injection of STZ combined with a high-fat diet.Serum and organs were used to detect the glucose and lipid metabolism PI3K/AKT/GS and endoplasmic reticulum stress PERK/ATF4/CHOP signaling pathways,and explore the effects of TZKP on T2DM endoplasmic reticulum.ResultsTZKP can significantly reduce the content of GLU(F<0.01),TG and TC(P<0.05,<0.01)in the serum of each model rat.Studies on related mechanisms have shown that TZKP can promote glucose metabolism by up-regulating the expression of glycogen synthesis-related protein GS(P<0.05),and can achieve lipid-regulating effects by regulating the LXRα/LCAT/CYP7A1 pathway(P<0.05,<0.01).Further experimental studies have shown that this mechanism of reducing blood sugar and regulating lipids is related to endoplasmic reticulum stress.By alleviating the key signal of endoplasmic reticulum stress PERK/ATF4/CHOP(P<0.05,<0.01),it can affect the expression of hypoglycemic and lipid-lowering target proteins,and then affect the glucose and lipid metabolism in the body,protect the islet cells,and promote the secretion and utilization of insulin.TZKP can also significantly reduce the secretion of related inflammatory factors IL6(P<0.05,<0.01),TNFα(P<0.01)and IL1β(P<0.01),and achieve anti-inflammatory efficacy.ConclusionTZKP has good hypoglycemic and lipid-lowering effects and its role in the prevention and treatment of T2DM.Its mechanism of action in the treatment of T2DM may be through endoplasmic reticulum stress affecting glucose and lipid metabolism,thereby alleviating insulin resistance.