Abstract:

Objective Peroxisome proliferator-activated receptor-γ co-activator 1(PGC-1α) is an important nuclear receptor co-activator, which was involved in regulating glycogenolysis, gluconeogenesis and the glucose utilization of the surrounding tissue. It also plays an important role in maintaining the balance of body energy metabolism, glucose and lipid metabolism. Our study was designed to explore the role of PGC-1α in the diabetes and insulin resistance by observing the changes of the PGC-1α mRNA in the liver, skeletal muscle, fat and pancreatic tissues of OLETF rats. Methods ① OLETF and LETO rats were fed with high sugar(10%) at the 8th week, and OLETF rats all became diabeties in the 18th week. ② Four rats of each group were sacrificed in the 8th and 28th week. Liver, skeletal muscle, fat and pancreatic tissues were collected and total RNA were extracted. PGC-1α mRNA expressions was analyzed by using real-time quantitative PCR. Results ① Body weight and TG level of OLETF rats increased with weeks of age dependent and were significant higher than those of same age of LETO rats from 14th week. After fasting and glucose loading, insulin levels of OLETF rats were also significant higher than that of the same age of LETO rats starting from 22nd week. ② At the 8th week, there were no significant difference in PGC-1αmRNA expression between OLETF and LETO rats in the liver, skeletal muscle, fat and pancreatic tissue. ③ At the 28th week, compared with the LETO rats, the PGC-1αmRNA expression of OLETF rats decreased significantly in the liver(0.040±0.006 vs 0.074±0.003, P=0.029) and pancreas(0.659±0.299 vs 1.610±0.091, P=0.029), but increased significantly in skeletal muscle tissues(0.192±0.065 vs 0.104±0.012, P=0.029). It also showed a downward trend in the adipose tissue(0.055±0.036 vs 0.161±0.124, P=0.100).
Conclusion OLETF rat showed insulin resistance and hyperglycemia, a typical pathological feature of early stage of type 2 diabetes at 28th week. The changes of PGC-1α mRNA expression in the liver, skeletal muscle, fat and pancreas of OLETF rat might be a compensatory response in the insulin resistance and hyperglycemia state of early stage of diabetes. It suggested that the changes of PGC-1α expression in the different tissues may be involved in the pathogenesis of insulin resistance and diabetes.

Key words: peroxisome proliferatoractivated receptor&gamma, co-activator 1;type 2 diabetes;insulin resistance;OLETF rat