| Objective: Type 2 diabetes mellitus is a kind of inferior clinical chronic inflammation. Skeletal muscle is the main point of injury to insulin activity in type 2 diabetes mellitus, so enhancing glucose metabolism in skeletal muscle is an important method. But the relations between insulin signaling in skeletal muscle of type 2 diabetes mellitus and inflammation is not completely clear yet. Related studies indicated that chronic inflammation can induce insulin resistance and type 2 diabetes mellitus by many ways whereas inflammation plays an important role by impact insulin signaling. Insulin receptor substrate 1 (IRS-1) is the line intersection of many signal transduction systems and is generally distributed in insulin sensitive tissues such as skeletal muscle intracytoplasm. Tumor necrosis factor (TNF-α)and interleukin-1β(IL-1β) can also be detected in skeletal muscle,and may have some relationship with isulin resistance and type 2 diabetes mellitus. Rosiglitizone (RSG)is a kind of 2,4-double-diketone thiazolidine chemical compound. It is a new euglycemic agent, which can enhance periphery tissues glucose uptake by the influence of insulin, depress insulin resistance in these tissues. Therefore , RSG can improve glucose and lipid metabolism. Recent studies show that RSG has anti-inflammatory effect. So this study set up rats model of insulin resistance by feeding SD rats with a high-sucrose and high-fat diet. Then set up model of type 2 diabetes mellitus by injecting them streptozocin (STZ) intraperitioneally. RSG were given to insulin resistance and type 2 diabetic rats, and investigate the role of IRS-1,TNF-αand IL-1βin periphery insulin resistance.Method: SD rats were randomized in 3 groups: normal control group (NC group),insulin resistance group(IR group),type 2 diabetic group(DM group).Feed the NC group with standard rat forage ; feed the IR group and DM group with high-sucrose and high-fat diet. After 8 weeks draw off 5 rats by random from each group and then assess the insulin sensitivity by high insulin euglycemic clamp technique. The IR group and DM group appeared insulin resistance. Then in order to damage part of pancreas we injected DM group with STZ 25mg/kg intraperitioneally, so they appeared hyperglycaemia. From 11th week, IR group was divided in two groups by random: IR group and insulin resistance group treated with RSG (TIR); DM group was divided in two groups by random: DM group and diabetic rats treated with RSG (TDM). From the same time on ,TIR group and TDM group were given RSG 2mg/kg/d by intragastric administration;NC group,IR group and DM group were given the same dose of distilled water. The therapy interference lasted 8 weeks and the hole expriment lasted 18 weeks. At the end of 18th week, we measure the weight of rats, get blood from heart and measure FBG by oxidizing enzyme method; measure FINS by radio immunoassay; measure TG, TC, LDL, HDL by automatic biochemistry analyzer. We separated some muscle from quadriceps femoris and inspect the expression of IRS-1,TNF-αand IL-1βby PCR.Results: (1)At the end of 8th week, IR group's blood glucose was higher then NC group ,but there is no significant difference(P>0.05);TG,TC and FIN was higher than NC group (P<0.05,P<0.05,P<0.01);glucose infusion rate (GIR)of IR group was significantly lower than NC group (P<0.01).Two weeks after DM group injected with STZ 25mg/kg intraperitioneally , blood glucose of DM group was significantly higher than NC group (P<0.01); FINS was lower than IR group but still higher than NC group (P<0.05);TG,TC higher than NC group (P<0.01)(.2)At the end of 18th week when the experiment is finished, the FBG of IR group had no difference compared with NC group; the FBG of DM group was higher than NC group (P<0.01) . FINS, TC, TG and LDL are all higher than NC group (P<0.01);DM group lossed body weight (P<0.01); the FINS,TC,TG and LDLof TIR group and TDM group lowered down than respective control group ( P<0.05 ,P<0.01).(3) Compared with NC group, the expression of IRS-1 gene was significantly lower in IR group and DM group (P<0.01),and increased after treatment by RSG(P<0.05); the expression of TNF-αwas higher in IR group and DM group than NC group (P<0.05;P<0.01),and decreased after treatment by RSG (P<0.05);the expression of IL-1βwas higher in IR group and DM group than NC group (P<0.01), and decreased after treatment by RSG(P<0.01).Conclusions:(1)Rats in IR group showed obesity, hyperlipid, hyperinsulinmia. We successfully assessed the insulin sensitivity by high insulin euglycemic clamp technique in rats fed with high sucrose and fat diet. IR was duplicated ,then type 2 diabetes was set up by injecting them STZ intraperitoneally. This model is accompanied with hyprglycemia,, hyperinsulinmia and insulin resistance .It is similar to type 2 diabetes of human. It is a very good model to be used to study the type 2 dibetes mellitus and its complications.(2) T2DM is a procedure of chronic inflammation, TNF-αand IL-1βinterfered insulin signal transduction of IRS-1. These manifest the importance of anti-inflammation at the beginning of type 2 diabetes mellitus.(3)RSG can amelioration metabolic disorder of diabetic rats and lessen inflammation action in skeletal muscle, and then enhance the recovery of insulin signaling. Using RSG has anti-inflammation effect, so to improve the sensitivity of insulin thereby cure T2DM.
|
PDF Full Text Request