The acute effects of resistin on glucose transport and fatty acid metabolism in rodent skeletal muscle
This thesis is an investigation of the effects of recombinant resistin on glucose transport (GT) and fatty acid (FA) metabolism in mature rodent skeletal muscle. The purpose of the current study was to (1) verify that resistin impairs GT, (2) determine whether these effects are dependent on FA availability (ie. 0 (FF: fat free) vs. 2 mM (HF: high fat) palmitate) and, (3) determine resistin's effect on resting FA metabolism, using an isolated rat soleus muscle model. We also examined if (1) resistin impairs insulin signalling transduction at the level of Akt and AS160 phosphorylation and, (2) whether this inhibition can be improved by the addition of (a) AICAR, an activator of AMPK and FA oxidation, or (b) myriocin (M) and fumonisin B1 (F), inhibitors of ceramide synthesis. From our results, resistin impaired insulin-stimulated GT, but only in the presence of HF which coincided with impairments of Akt-ser473 and thr-308 phosphorylation. The addition of AICAR F and M were able to improve this impairment. Surprisingly, no effect of resistin was observed in FA metabolism per se. We conclude that resistin's mechanism of action in the impairment of GT and insulin-signalling with HF may involve early inhibition of AMPK or increased intramuscular accumulation of ceramides.