Studies On The Mechanism Of Pioglitazone In Improving Insulin Resistance Of Type1Diabetic Rats

Diabetes (diabetes mellitus, DM) is a kind of metabolic disease associated withinsulin secretion or the role of defects, which is characterized by chronichyperglycemia caused by a variety of causes. The main clinical symptom is moredrinks, polyphagia, polyuria, loss of weight. But the exact pathogenesis of type1diabetes is still not fully elucidated, which resulted in a lack of effective drugs fortype1diabetes treatment. Establishing the animal model of type1diabetes andStudying on the treatment effects of pioglitazone (PIO) can provide us with areference for clinical therapy of type1diabetes.In this study we use the alloxan to induce type1diabetic rat model. After a weekof normal diet feeding, six rats were selected randomly from the30rats as normalcontrol group (NC,6rats), the remaining rats were induced by intraperitoneallyinjection of alloxan after fasting24hours. After72hours and a week determinatingthe rat tail fasting blood sugar, two blood glucose levels are higher than16.7mmol/Lfor successful type1diabetic rat model. The model rats were randomly divided intodiabetic model group (DM,6rats) and pioglitazone treatment group (PIO,6rats).After two weeks of drug intervention, at first, all rats were weighed and dissected forthe biochemical analysis. Then we weighed all livers and calculated liver index.Content of the following components were measured: fasting blood glucose (FBG),serum triglycerides (TG), free fatty acid (FFA), trace malondialdehyde (MDA); Theliver triglycerides (TG), trace malondialdehyde (MDA).Experimental results show that the body weight, liver index, serum levels of FBG,TG, FFA and MDA, and hepatic TG and MDA levels increased significantly in DMrats, which shows a statistical significant difference comparing with NC (p <0.01).Liver fibrosis, fat lesions, hepatomegaly and oxidative stress appeared in thepathological section. At the same time, the levels of these components in PIO ratswere lower than DM, but still higher than that of NC, which both show a statisticalsignificance comparing with DM (p <0.01). The oxidative stress of liver can hardlybe observed.This study shows that the type1diabetic rat model was established successfullyafter72hours by intraperitoneally injection of alloxan. The modeling methodsimulated evolution process of diabetic patients accompanying by disease symptoms; and the method has these characteristics of high success rate, low cost, goodrepeatability and easy manipulation. Pioglitazone (PIO) can improve type1diabetesto a certain extent. Since PIO can increase the body tissue insulin sensitivity, improveinsulin resistance (IR) and lower blood sugar through lowering the serum FFA levelsand improving oxidative stress and inflammation, we predict these may be themechanisms of effects of the PIO.