Abstract:
: Type-2 diabetes is mediated by defects in either insulin secretion or insulin action. In an effort to identify extracts that may stimulate glucose uptake, similar to insulin, a high throughput-screening assay for measuring glucose uptake in skeletal muscle cells was established. During the screening studies to discover novel antidiabetic compounds from microbial resources a Streptomyces strain PM0324667 (MTCC 5543, the Strain accession number at Institute of Microbial Technology, Chandigarh, India), an isolate from arid soil was identified which expressed a secondary metabolite that induced glucose uptake in L6 skeletal muscle cells. By employing bioactivity guided fractionation techniques, a tri-substituted simple aromatic compound with anti-diabetic potential was isolated. It was characterized based on MS and 2D NMR spectral data and identified as NFAT-133 which is a known immunosuppressive agent that inhibits NFAT-dependent transcription in vitro. Our investigations revealed the antidiabetic potential of NFAT-133. The compound induced glucose uptake in differentiated L6 myotubes with an EC50 of 6.3 ± 1.8 μM without activating the peroxisome proliferator-activated receptor-γ. Further, NFAT-133 was also efficacious in vivo in diabetic animals and reduced systemic glucose levels. Thus it is a potential lead compound which can be considered for development as a therapeutic for the treatment of type-2 diabetes. We have reported herewith the isolation of the producer microbe, fermentation, purification, in vitro, and in vivo antidiabetic activity of the compound.
journal_name
AMB Expressjournal_title
AMB Expressauthors
Kulkarni-Almeida AA,Brahma MK,Padmanabhan P,Mishra PD,Parab RR,Gaikwad NV,Thakkar CS,Tokdar P,Ranadive PV,Nair AS,Damre AA,Bahirat UA,Deshmukh NJ,Doshi LS,Dixit AV,George SD,Vishwakarma RA,Nemmani KV,Mahajan GBdoi
10.1186/2191-0855-1-42subject
Has Abstractpub_date
2011-11-21 00:00:00pages
42issue
1issn
2191-0855pii
2191-0855-1-42journal_volume
1pub_type
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