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Effect of Imeglimin on gene expression of renal cortex from diabetic mice

ABSTRACT: Imeglimin is an oral hypoglycemic agent marketed from Japan and has shown glucose-lowering effects in Japanese patients with type 2 diabetes in TIMES trials. However, it is not well known whether Imeglimin can affect diabetic kidney disease (DKD). To clarify this, we investigated the potential association between the effects of Imeglimin and DKD by using diabetic mice (DM) and cultured endothelial cell. Administration of Imeglimin significantly lowered urinary albumin excretion in DKD, but did not significantly affect blood glucose and glycated albumin. RNA sequencing analysis of renal cortex indicated the upregulation of anti-oxidative, oxidative phosphorylation and AMPK signaling pathway and downregulation of inflammation, atherosclerosis and reactive oxygen species. Additionally, Imeglimin decreased the mRNA expressions of TNF-α, F4/80 and Fibronectin on renal cortex of DKD. In parallel with the findings that Imeglimin reduced the protein expression of Fibronectin on renal cortex of DKD, renal histological fibrosis was significantly increased in DM compared with NDM, which was significantly reduced by Imeglimin. In vitro study, HG induced the mRNA expressions of Nlrp3, Vcam-1 and NOX4, which were downregulated by Imeglimin. These results suggest that Imeglimin could improve albuminuria associated with partial suppression of inflammatory and fibrotic markers in DKD.

ORGANISM(S): Mus musculus

PROVIDER: GSE344280 | GEO | 2026/08/24

REPOSITORIES: GEO

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