N Saleh1, H E Elayan1, M Zihlif1. 1. University of Jordan, Faculty of Medicine, Department of Pharmacology, Amman, Jordan.
Abstract
BACKGROUND: 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. OBJECTIVES: 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). ANIMALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.
BACKGROUND: 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. OBJECTIVES: 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). ANIMALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.
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