Browsing by Author "Rawat, Kajal"

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    L-Methionine prevents ?-cell damage by modulating the expression of Arx, MafA and regulation of FOXO1 in type 1 diabetic rats
    (Elsevier GmbH, 2021-12-03T00:00:00) Navik, Umashanker; Rawat, Kajal; Tikoo, Kulbhushan
    L-Methionine (L-Met) is an essential sulphur-containing amino acid having a vital role in various key cellular processes. Here we investigated the effect of L-Met on streptozotocin-induced ?-cell damage model of diabetes mellitus in Sprague Dawley rats. At the end of study biochemical parameters, immunoblotting, qRT-PCR and ChIP-qPCR are performed. L-Met was administered orally (250 and 500 mg/kg/day) to diabetic animals for 8 weeks improved plasma glucose and insulin levels. Pancreas immunohistochemistry showed significant increase in insulin expression, decrease in glucagon and Bax expression. Interestingly, L-Met inhibited the expression of Arx; upregulated MafA and FOXO1 which play a critical role in the maintenance of ?-cell identity. Our data also showed a decrease in H3K27me3 and an increase in H3K4me3 (�bivalent domain� alteration) in diabetic rats and these recovered by L-Met. Furthermore, the chromatin-immunoprecipitation assay showed a decreased enrichment of H3K27me3 on the promoter of the FOXO1 gene in diabetic rats and L-Met prevents this decrease. Our results showed the first evidence of the involvement of H3K27me3 in regulating the expression of the FOXO1 gene and the prevention of ?-cell injury by L-Met treatment. In conclusion, we report the involvement of L-Met in the modulation of ?-cell identity marker (Arx), ?-cell identity marker (MafA) and regulation of FOXO1 by histone methylation marks for the first time. We are of the opinion that this employed as a novel therapeutic approach for mitigating diabetes-induced ?-cell death. � 2021 Elsevier GmbH