NFAT-133 increases glucose uptake in L6 myotubes by activating AMPK pathway.

NFAT-133 is an aromatic compound with cinammyl alcohol moiety, isolated from streptomycetes strain PM0324667. We have earlier reported that NFAT-133 increases insulin stimulated glucose uptake in L6 myotubes using a PPARγ independent mechanism and reduces plasma or blood glucose levels in diabetic mice. Here we investigated the effects of NFAT-133 on cellular signaling pathways leading to glucose uptake in L6 myotubes. Our studies demonstrate that NFAT-133 increases glucose uptake in a dose- and time-dependent manner independent of the effects of insulin. Treatment with Akti-1/2, wortmannin and increasing concentrations of insulin had no effect on NFAT-133 mediated glucose uptake. NFAT-133 induced glucose uptake is completely mitigated by Compound C, an AMPK inhibitor. Further, the kinases upstream of AMPK activation namely; LKB-1 and CAMKKβ are not involved in NFAT-133 mediated AMPK activation nor does the compound NFAT-133 have any effect on AMPK enzyme activity. Further analysis confirmed that NFAT-133 indirectly activates AMPK by reducing the mitochondrial membrane potential and increasing the ratio of AMP:ATP. Copyright © 2015 Elsevier B.V. All rights reserved.

Citation

Chandni S Thakkar, Abhijeet S Kate, Dattatraya C Desai, Asit Ranjan Ghosh, Asha A Kulkarni-Almeida. NFAT-133 increases glucose uptake in L6 myotubes by activating AMPK pathway. European journal of pharmacology. 2015 Dec 15;769:117-26

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PMID: 26546724

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