Integra

Introduction

Rosiglitazone is an insulin sensitizer acting as a synthetic ligand of peroxisome proliferator-activated receptor gamma (PPARγ). PPARγis a ligand-dependent transcription factor that regulates transcription of the genes involving in glucose and lipid metabolism. This receptor play a central role in modulating glucose and lipid metabolism. Glucose transporter 4 (GLUT4) distributes in muscle and adipose tissues and plays an important role in taking up and utilizing glucose. In order to research the actions of rosiglitazone and exercise on glucose metabolism, we selected PPARα, PPARγ and GLUT4 as targets to determined.

Methods

Firstly, to established the model of laboratory rodents,the 3-4 weeks old NOD mice were treated with rosiglitazone for 12 weeks or trained by treadmill exercise for 12 weeks. We observed their appearance, body weight and belly fat to decide the difference between the treated mice and the controlled mice. Secondly, the concentration of serum insulin, glucose, triacylglycerols(TG) , total cholesterol(TC), HDL- cholesterol(HDL-C) and LDL-cholesterol(LDL-C) were tested. Thirdly, the mRNA expression of PPARα, PPARγ and GLUT4 genes was analysed by RT-PCR.

Results

For the controlled mice, their fur looked fade and dishevelled, body weight decreased and belly fat withered. For the treated mice, they are spirited, and their belly fat did not wither. There were marked differences between the treated mice and the controlled mice. The level of serum insulin of the controlled mice was higher. The level of blood glucose of the controlled mice was significant higher than that of the treated mice. The TC,TG and LDL-C of the controlled mice were bad. The mRNA expression of PPARα had no difference between the treated and the controlled groups. Compared with control, the mRNA expression of PPARγ in liver, muscle and adipose tissue was increased 1- to 2-fold after the mice were treated with rosiglitazone or trained. The level of GLUT4 mRNA of the treated mice was over 1-fold higher than that of the controlled mice in muscle and adipose tissue.

Conclusion

Rosiglitazone and aerobic exercise regulate glucose metabolism by activating PPARγ expression selectly, and PPARγ mediates GLUT4 expression sequentially. This is a possible path through which insulin sensitizer and moderate endurance exercise improve diabetes.

References

10.P.Fernando,A.Bonen,L.hoffman-Goetz(1993). Can.J.Physiol,Pharmacol。71,854-857.
11.Berger J. , David E.M(2002).Annu.Rev.Med.53,409-435.
12.Bryan F.Burkey,Mei Dong,Karen Gagen,et al(2000).Metabolism,49,1301-1308.
13.Miyazaki Y, Glass L, Triplit C, et al(2001).Diabetologia,44(12),2210-2219.
14.Mayerson AB, Hundal RS, Dufour S,et al(2002). Diabetes,51(3),797-802.
15.Cecilia A,Hifmann,Charles W, et al(1992).Endocrinology,130,735-740..
16.Fiona M,Campbell,Ray Kozak, et al(2002).The Journal of Biological Chemistry,277,4098-4103.
8. D.Kramer,R.Shapiro,A.Adler, et al(2001). Metanolism,50,:1294- 1300.