Effects Of Long-Term High-protein Diet On The Expression Of IRS2 And GLUT2 In Liver Of Diet Induced Obesity Rat

BackgroundThe type 2 diabetes mellitus (T2DM) is a result of long-term effects of genetic and environmental factors, and insulin resistance and insulin deficiency are two important mechanisms of the disease. Obesity can affect many parts of the insulin signal pathway, reducing the effects of insulin, reducing insulin sensitivity, leading to abnormal glucose regulation. Long-term high-fat diet could lead to obesity, insulin resistance, and it is a risk factor of type 2 diabetes group. It is inconclusive that whether long-term high protein diet would lead to diabetes mellitus in obese patients. Most animal experiments and clinical studies shows that long-term high-protein diet could reduce body weight, improve glucose control. And it is an effective dietary intervention. However, recent epidemiological investigation showed thatthe incidence of T2DM increased rapidly with the dietary protein increased, which was a challenge to good affect to blood sugar of the long-term high-protein diet.It is very complex that of the dietary protein on glucose metabolism and insulin sensitivity. It may be affected by the genetic characteristics, nutritional status, the type of protein, form, time and some other factors. The present studies are mostly limited to normal or diabetic individuals. It is uncommon to study long-term high-protein diet on obese individuals'insulin sensitivity, not to mention to study the mechanisms of the long-term high-protein diet affecting the insulin resistance. The liver is an important organ of energy metabolism, is the main target organ of the insulin and play a very important role in glucose metabolism of the whole body. Studies have shown that the hepatic insulin resistance played an important role in T2DM patients leading by obesity and/or excess nutrients.In the insulin-target tissues in obesity and T2DM patients, the decresed insulin sensitivity, the decreased IRSs contends and the decresed signals regulating the metablism of sugar and lipid, finally lead to metablic disorders. IRS2 is widely distributed, mainly in the liver andβcells of pancreatic islet. It played a major role in the promotion of the glycogen synthesis and the suppression of glucose output in liver. The GLUT2 is mainly distributed in liver, kidney, small intestine andβcells of pancreatic islet. GLUT2 of liver consist of more than 97% of glucose transporter protein.For this, we choose the IRS2 and the GLUT2 in liver as the objects to study the effction of long-term high protein diet mechanisms of insulin sensitivity on diet-reduced obesity rats.ObjectiveThe aim of this study is to observe the IRS2 and the GLUT2 expression in livers of nutitional obesity rats given a long-term normal-caloric and high-protein diet and then to explore the mechanisms of on long-term high-protein diet on insulin resistance.MethodsDiet-induced obesity rat models were established by feeding Wistar rats (21 days old) high calorie and high fat diet for 14 weeks. The obesity male rats were randomly divided into three groups:the high-protein diet group (HP, n=12), the high-fat diet group (HF, n=11), and the normal chow group (NC, n=11). The total calorie ingestion of each rat per day was similar and was maintained for 24 weeks. The mRNA and protein expression of IRS2 and GLUT2 in liver were studied by RT-PCR and western blot method after executing the rats.Results1 The mRNA expression of IRS2 in liver:The ratio of IRS2 to internal reference of the light gray:the HP group(0.99±0.07) was significantly higher than the NC group(0.83±0.07) (P<0.05) and the HF group (0.65±0.09) (P<0.01),and was higher by 15% and 52% than that of the NC group and HF group.2 Theprotein expression of IRS2 in liver:The ratio of IRS2 to internal reference of the light gray:the HP group (1.18±0.049) was significantly higher than the NC group (0.95±0.08) (P<0.05) and the HF group (0.68±0.045) (P<0.01), and was higher by 24% and 74% than that of the NC group and HF group.3 The expression mRNA of GLUT2 in liver:The ratio of GLUT2 to internal reference of the light gray:the HP group (0.63±0.059) was significantly higher than the NC group (0.51±0.058) (P<0.05) and the HF group (0.14±0.007) (P<0.01), and was higher by 24% and 71% than that of the NC group and HF group.4 The expression protein of GLUT2 in liver:The ratio of GLUT2 to internal reference of the light gray:the HP group (0.84±0.05) was significantly higher than the NC group (0.67±0.05) (P<0.05) and the HF group (0.49±0.04) (P<0.01) and was higher by 25% and 352% than that of the NC group and HF group.Conclusion:Compared with the normal diet, long-term high-protein diet can upregulate the expression of IRS2 and GLUT2 in liver ofdiet-induced obesity rats. It may be one of the mechanisms of long-term high-protein diet to improve the insulin sensitivity of diet-induced obesity rats.