Analysis Of The Expression Characteristics Of Gpnmb And PI3K/Akt/mTOR Pathway-Related Proteins In Type 2 Diabetic Mice

According to statistics,the number of people with type 2 diabetes mellitus(T2DM)will reach 592 million worldwide in 2030,and diabetes mellitus(DM)has become a chronic epidemic disease worldwide and one of the most serious public health problems in the 21 st century.The prevalence of type 2 diabetes is 3-7 times higher in obese people than in normal people,and is one of the important risk factors for the development of type 2 diabetes.It has been found that Gpnmb(Glycoprotein non-metastatic melanoma protein B),an important regulator of adipogenesis secreted by the liver,and the PI3 K / Akt / mTOR pathway in response to insulin signaling may be related to lipid metabolism.However,there are few studies on Gpnmb and PI3 K /Akt / mTOR pathway in type 2 diabetes.The purpose of this study was to observe the expression characteristics of Gpnmb and PI3 K / Akt / mTOR pathways in type 2diabetic mice,and to provide more scientific basis for the pathogenesis and treatment of type 2 diabetes.Male C57 BL / 6J mice(6 weeks old)were fed a high-fat diet(HFD)for 15 weeks to construct a DIO(Diet-Induced Obesity)mouse model.During the modeling period,fasting blood glucose and body weight were monitored regularly.After modeling,the average body weight of mice in the model group was significantly higher than that in the normal control group(P < 0.01).Fasting plasma glucose(FPG)was greater than 7.0 mmol / L,and 2-h PG ≥ 11.1 mmol / L during oral glucose tolerance test(OGTT).After four weeks of administration,the liver and white adipose tissue(WAT)were dissected and collected.After weighing,they were fixed in 4 % paraformaldehyde and frozen at-80 °C,respectively.Blood samples were collected for blood biochemical tests before dissection.Blood samples were collected for blood biochemical tests before dissection.HE staining,oil red O staining and Masson trichrome staining were used to observe the pathological changes of liver and adipose tissue.Immunohistochemical staining and real-time fluorescence quantitative PCR were used to detect the expression position and expression level of the target protein and the relative m RNA expression of the target gene.1.HFD induced changes in basic physiological data,liver pathological damage and WAT cell enlargement in type 2 diabetic mice : Compared with the normal control group,the body weight,liver coefficient,body fat ratio,PFG,serum ALT,AST,LDL,TC and TG levels of the model group were increased,and the difference was statistically significant(P < 0.05 or P < 0.01).The serum insulin level was decreased,and the difference was statistically significant(P < 0.05).Liver cells showed obvious steatosis and fibrous hyperplasia,and WAT cells increased,with statistically significant differences(P < 0.01).Compared with the model group,the body weight,liver coefficient,body fat ratio,PFG,and serum ALT,LDL,and TC levels of the mice in the treatment group decreased,and the difference was statistically significant(P < 0.05 or P < 0.01).The serum insulin level increased,but the difference was not statistically significant(P > 0.05).The steatosis and fibrous hyperplasia of hepatocytes were reduced,and the cells of WAT were decreased,the difference was statistically significant(P < 0.01).2.The expression of Gpnmb in the liver and WAT of type 2 diabetic mice was up-regulated : Compared with the normal control group,the protein expression and m RNA expression of Gpnmb and CD44 in the liver and WAT of the model group were increased,and the difference was statistically significant(P < 0.05 or P < 0.01);compared with the model group,the protein expression and m RNA expression of Gpnmb and CD44 in the liver and WAT of the treatment group were decreased,and the difference was statistically significant(P < 0.05 or P < 0.01).3.The expression of PI3 K / Akt / mTOR pathway-related proteins in the liver and WAT of type 2 diabetic mice was up-regulated : Compared with the normal control group,the protein expression and m RNA expression of PI3 K,Akt,mTOR and SREBP1 c in the liver and WAT of the model group showed a significant increasing trend.Compared with the model group,the protein expression and m RNA expression of PI3 K,Akt,mTOR and SREBP1 c in the liver and WAT of the treatment group showed a significant decreasing trend.Compared with the normal control group,the m RNA expression of FASN,Acl,Acc,Acs and Lce in the liver of the model group increased,and the difference was statistically significant(P < 0.05 or P < 0.01).The m RNA expression of FASN and Lce in WAT of the model group increased,and the difference was statistically significant(P < 0.05 or P < 0.01).Compared with the model group,the m RNA expression of FASN,Acs and Lce in the liver of the treatment group decreased,and the difference was statistically significant(P < 0.05 or P < 0.01).The m RNA expression of FASN in WAT of the treatment group decreased,and the difference was statistically significant(P < 0.05 or P < 0.01).The results showed that HFD induced changes in basic physiological data,liver pathological damage and WAT cell enlargement in type 2 diabetic mice.The expression levels of Gpnmb and PI3 K / Akt / mTOR pathway-related proteins and fatty acid metabolism enzyme-related genes(FASN,Acl,Acc,Acs,Lce)in the liver and WAT of type 2 diabetic mice were up-regulated.