Forskolin attenuates the action of insulin on the Akt-mTOR pathway in human skeletal muscle.

Forskolin (FSK) is capable of both stimulating and inhibiting the intracellular signaling pathways of protein synthesis tissues other than skeletal muscle. The purpose of this investigation was to determine if FSK administration affects various elements of the protein kinase B (Akt)-mammalian target of rapamycin (mTOR) pathway in human skeletal muscle. Ten (n = 10) healthy, young (21.6 +/- 1.3 years), nonobese (body mass index = 25.5 +/- 3.5 kg.m-2), recreationally active males were selected for participation. Following an 8 h fast, 2 muscle biopsies of the vastus lateralis were performed. The samples were sectioned and exposed to 4 in vitro treatment conditions: basal, FSK, insulin (INS), and FSK+INS. The samples were then analyzed for total and phosphorylated levels of Akt, mTOR, S6 kinase (S6K1), and 4E binding protein (4EBP1). Akt phosphorylation was significantly greater in the INS-treated samples compared with the basal and FSK conditions (p = 0.007). Furthermore, the ratio of phosphorylated Akt to total Akt (P/T) was higher in the INS samples compared with the basal and FSK samples (p = 0.001). There were no differences in mTOR phosphorylation among the 4 groups; however, total mTOR was significantly greater in the FSK+INS group (p = 0.006). There were also no differences in phosphorylated or total levels of S6K1 among the 4 groups. However, 4EBP1 phosphorylation was significantly greater in the INS-treated samples compared with the basal (p = 0.003) and FSK (p = 0.004) treatments. There were no differences in the ratio of phosphorylated 4EBP1 to total 4EBP1 (P/T) among the 4 groups. These results indicate that FSK does not activate the Akt-mTOR pathway in human skeletal muscle; however, these results suggest that FSK may inhibit the actions of INS on this pathway.