Avtor/Urednik		Kolnes, AJ; Ingvaldsen, A; Kreft, M; Zorec, R
Naslov		Caffeine and theophylline block insulin-stimulated glucose uptake and PKB phosphorylation in rat skeletal muscles
Tip		članek
Vir		Acta Physiol (Oxf)
Vol. in št.		Letnik 200, št. 1
Leto izdaje		2010
Obseg		str. 65-74
Jezik		eng
Abstrakt		Aim: Caffeine and theophylline inhibit phosphatidylinositol 3-kinase (PI3-kinase) activity and insulin-stimulated protein kinase B (PKB) phosphorylation. Insulin-stimulated glucose uptake involves PI3-kinase/PKB, and the aim of the present study was to test the hypothesis that caffeine and theophylline inhibit insulin-stimulated glucose uptake in skeletal muscles. Methods: Rat epitrochlearis muscles and soleus strips were incubated with insulin and different concentrations of caffeine and theophylline for measurement of glucose uptake, force development and PKB phosphorylation. The effect of caffeine was also investigated in muscles stimulated electrically. Results: Caffeine and theophylline completely blocked insulin-stimulated glucose uptake in both soleus and epitrochlearis muscles at 10 mm. Furthermore, insulin-stimulated PKB Ser(473) and Thr(308) and GSK-3beta Ser(9) phosphorylation were blocked by caffeine and theophylline. Caffeine reduced and theophylline blocked insulin-stimulated glycogen synthase activation. Caffeine stimulates Ca(2+) release and force development increased rapidly to 10-20% of maximal tetanic contraction. Dantrolene (25 mum), a well-known inhibitor of Ca(2+)-release, prevented caffeine-induced force development, but caffeine inhibited insulin-stimulated glucose uptake in the presence of dantrolene. Contraction, like insulin, stimulates glucose uptake via translocation of glucose transporter-4 (GLUT4). Caffeine and theophylline reduced contraction-stimulated glucose uptake by about 50%, whereas contraction-stimulated glycogen breakdown was normal. Conclusion: Caffeine and theophylline block insulin-stimulated glucose uptake independently of Ca(2+) release, and the likely mechanism is via blockade of insulin-stimulated PI3-kinase/PKB activation. (Abstract truncated at 2000 characters)
Deskriptorji		MUSCLE, SKELETAL CAFFEINE THEOPHYLLINE PHOSPHATIDYLINOSITOLS PROTEIN KINASES PHOSPHORYLATION INSULIN GLUCOSE GLYCOGEN RATS, WISTAR