THE EFFECT OF SALBUTAMOL ON PGC-1 α AND GLUT4 mRNA EXPRESSION IN THE LIVER AND MUSCLE OF ELDERLY DIABETIC MICE

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) plays an important role in the regulation of cellular energy metabolism, and it is involved in obesity and type 2 diabetes mellitus (T2DM). Its expression is elevated in the liver of T2DM mouse models. Literature reports show that chronic β2 stimulation improved insulin sensitivity in T2DM. We aimed to test the hypotheses that chronic β2 stimulation-induced improvement in insulin sensitivity involves changes in the expression of PGC-1α and glucose transporter 4 (GLUT4). We fed a locally inbred, 8 months old mice, a high fat diet (HFD) to induce diabetes. These mice gained weight and became insulin resistant. The β2 agonist salbutamol had a beneficial effect on both glucose tolerance and insulin sensitivity after 4 weeks. Salbutamol beneficial effect persisted after 4 weeks of its discontinuation. HFD caused an up regulation of the hepatic PGC-1 α expression by 5.23 folds (P< 0.041) and salbutamol reversed this effect and caused a down regulation by 30.3 folds (P< 0.0001). PGC-1 α and GLUT4 expression in the muscle was not affected by salbutamol (P> 0.05). Down regulation of the liver's PGC-1 α contributes to the beneficial effect of the chronic β2 stimulation on glucose tolerance and insulin sensitivity in T2DM mice.