Fermentation, Isolation, Structure, and Antidiabetic Activity of NFAT-133 produced by Streptomyces strain PM0324667

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.

Some Functional Properties of khambir, an Ethnic Fermented Cereal-Based Food of Western Himalayas

“…Over 100 glycosidase inhibitors have been isolated from plants and microorganisms (Pandey et al, 2013). A group of microbes originating from β-glucosidase inhibitors like acarbose, voglibose, valienamine, adiposin-1, and trestatin-B are commercially exploited as anti-diabetic drugs which can reduce sugar digestion (undigested resistant starch) and assimilation into the body (Kulkarni-Almeida et al, 2011). Both khambir preparations, YAK and BAK exhibited 18 and 29% inhibition of β-glucosidase activity (Figure 2A), establishing them as a useful diabetic diet.…”

Molecular Identification of Selected Streptomyces Strains Isolated from Mexican Tropical Soils and their Anti-Candida Activity

“…The other two strains, S. parvisporogenes S2A-04 and S. angustmyceticus S6A-03, come from soils with higher acidity. In 2011, Kulkarni-Almeida [32] isolated S. parvisporogenes PM0324667 from a neutral to alkaline sandy soil (Rajasthan, India) [33]. Pithakkit [34] reported the isolation of S. angustmyceticus NR8-2 from slightly acidic soils from palm tree plantations in the south of Thailand [35].…”

Antidiabetic and Antioxidant Potential of GancidinW from Streptomyces Paradoxus VITALK03

“…has been reported to exhibit specific inhibitory activity against Nacetyl-glucosaminidase (Imada, 2005). The novel antidiabetic compound NFAT-133 extracted from Streptomyces strain PM0324667 was reported to induce glucose uptake in L6 skeletal muscle cells [33]. NIFTA has been reported to be effectively reduced systemic glucose levels in diabetic animals.…”