NPC86 Increases LncRNA Gas5 In Vivo to Improve Insulin Sensitivity and Metabolic Function in Diet-Induced Obese Diabetic Mouse Model DOI Open Access

Anna Kharitonova,

Rekha Patel, Brenna Osborne

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3695 - 3695

Published: April 14, 2025

In the United States, an estimated 38 million individuals (10% of population) have type 2 diabetes mellitus (T2D), while approximately 97.6 adults (38%) prediabetes. Long noncoding RNAs (lncRNAs) are critical regulators gene expression and metabolism. We were first to demonstrate that lncRNA Growth Arrest-Specific Transcript 5 (GAS5 (human)/gas5 (mouse)) is decreased in serum T2D patients established GAS5 as a biomarker for diagnosis onset prediction, now validated by other groups. further demonstrated depletion impaired glucose uptake, insulin receptor levels, inhibited signaling human adipocytes, highlighting its potential therapeutic target T2D. To address this, we developed NPC86, small-molecule compound stabilizes disrupting interaction with UPF-1, RNA helicase involved nonsense-mediated decay (NMD) regulates stability. NPC86 increased (IR) enhanced signaling, improved uptake vitro. this study, tested efficacy vivo diet-induced obese diabetic (DIOD) mouse model, treatment elevated gas5 tolerance, sensitivity, no observed toxicity or weight changes. A transcriptomics analysis adipose tissue revealed upregulation metabolic pathways, including oxidative phosphorylation glycolysis, inflammatory pathways downregulated. These findings highlight NPC86’s

Language: Английский

NPC86 Increases LncRNA Gas5 In Vivo to Improve Insulin Sensitivity and Metabolic Function in Diet-Induced Obese Diabetic Mouse Model DOI Open Access

Anna Kharitonova,

Rekha Patel, Brenna Osborne

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3695 - 3695

Published: April 14, 2025

In the United States, an estimated 38 million individuals (10% of population) have type 2 diabetes mellitus (T2D), while approximately 97.6 adults (38%) prediabetes. Long noncoding RNAs (lncRNAs) are critical regulators gene expression and metabolism. We were first to demonstrate that lncRNA Growth Arrest-Specific Transcript 5 (GAS5 (human)/gas5 (mouse)) is decreased in serum T2D patients established GAS5 as a biomarker for diagnosis onset prediction, now validated by other groups. further demonstrated depletion impaired glucose uptake, insulin receptor levels, inhibited signaling human adipocytes, highlighting its potential therapeutic target T2D. To address this, we developed NPC86, small-molecule compound stabilizes disrupting interaction with UPF-1, RNA helicase involved nonsense-mediated decay (NMD) regulates stability. NPC86 increased (IR) enhanced signaling, improved uptake vitro. this study, tested efficacy vivo diet-induced obese diabetic (DIOD) mouse model, treatment elevated gas5 tolerance, sensitivity, no observed toxicity or weight changes. A transcriptomics analysis adipose tissue revealed upregulation metabolic pathways, including oxidative phosphorylation glycolysis, inflammatory pathways downregulated. These findings highlight NPC86’s

Language: Английский

Citations

0