2. Academic Validation
  3. NFAT-133 increases glucose uptake in L6 myotubes by activating AMPK pathway

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

  • Eur J Pharmacol. 2015 Dec 15:769:117-26. doi: 10.1016/j.ejphar.2015.11.006.
Chandni S Thakkar 1,  Abhijeet S Kate 2,  Dattatraya C Desai 3,  Asit Ranjan Ghosh 4,  Asha A Kulkarni-Almeida 5
Affiliations

Affiliations

  • 1 Screening-Metabolic Disorders Translational Unit, Piramal Enterprises Limited, 1A-Nirlon Complex, Off Western Express Highway, Goregaon (East), Mumbai 400063, Maharashtra, India.
  • 2 Department of Natural Products, Piramal Enterprises Limited, 1A-Nirlon Complex, Off Western Express Highway, Goregaon (East), Mumbai 400063, Maharashtra, India.
  • 3 Department of Medicinal Chemistry, Piramal Enterprises Limited, 1A-Nirlon Complex, Off Western Express Highway, Goregaon (East), Mumbai 400063, Maharashtra, India.
  • 4 Centre for Infectious Diseases & Control, School of BioSciences and Technology, VIT University, Vellore 632014, Tamil Nadu, India.
  • 5 Screening-Metabolic Disorders Translational Unit, Piramal Enterprises Limited, 1A-Nirlon Complex, Off Western Express Highway, Goregaon (East), Mumbai 400063, Maharashtra, India. Electronic address: asha_almeida@yahoo.co.in.
PMID: 26546724 DOI: 10.1016/j.ejphar.2015.11.006
Abstract

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.

Keywords

AMP/ATP ratio; AMPK; Glucose uptake; L6 myotubes; Mitochondrial membrane potential; NFAT-133.

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