| Autor: |
Kulkarni-Almeida AA; Piramal Life Sciences Limited, 1-Nirlon Complex, Off Western Express Highway, Goregaon (East), Mumbai-400063, Maharashtra State, India. girish.mahajan@piramal.com., 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 GB |
| Jazyk: |
angličtina |
| Zdroj: |
AMB Express [AMB Express] 2011 Nov 21; Vol. 1 (1), pp. 42. Date of Electronic Publication: 2011 Nov 21. |
| DOI: |
10.1186/2191-0855-1-42 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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