Similarities and Differences in the Intestinal Actions of Metformin and Imeglimin
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PROVIDER: PRJNA1298845 | ENA |
REPOSITORIES: ENA
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Project description:We investigated the intestinal actions of metformin and imeglimin by transcriptomic profiling. Bulk RNA-seq was performed on intestinal tissues from C57BL/6J mice after single or chronic drug administration, and single-cell RNA-seq was conducted on colon samples after chronic treatment.
2025-09-01 | GSE304061 | GEO
Project description:To investigate the effects of imeglimin and metformin on islet cells in db/db mice, we isolated pancreatic islets from db/db mice treated with/without imeglimin and metformin or db/+ mice.
2023-06-19 | GSE228726 | GEO
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| S-EPMC12515779 | biostudies-literature
Project description:Aims/Introduction: Metformin treatment for hyperglycemia in pregnancy (HIP) beneficially improves maternal glucose metabolism and reduces perinatal complications. However, metformin could impede pancreatic β cell development via impaired mitochondrial function. A new anti-diabetes drug imeglimin, developed based on metformin, improves mitochondrial function. Here we examine the effect of imeglimin on β cell differentiation using human induced pluripotent stem cell (iPSC)-derived pancreatic islet-like spheroid (SC-islet) models. Materials and Methods: Human iPSCs are differentiated into SC-islets by three-dimensional culture with and without imeglimin or metformin. Differentiation efficiencies of SC-islets were analyzed by flow cytometry, immunostaining, quantitative PCR, and insulin secretion assay. RNA sequencing and oxygen consumption rate were obtained for further characterization of SC-islets. SC-islets were cultured with proinflammatory cytokines, in part mimicking the uterus environment in HIP. Results: Metformin perturbed SC-islet differentiation while imeglimin did not alter it. Furthermore, imeglimin enhanced the gene expressions of β cell lineage markers. Maintenance of mitochondrial function and optimization of TGF-β and Wnt signaling were considered potential mechanisms for augmented β cell maturation by imeglimin. In the presence of proinflammatory cytokines, imeglimin ameliorated β cell differentiation impaired by cytokines and metformin. Conclusions: Imeglimin does not perturb differentiation of SC-islet cells and rather enhances gain in β cell identity gene sets in contrast to metformin. This may lead to the improvement of in vitro β cell differentiation protocols.
2025-01-20 | GSE242776 | GEO
Project description:To further understand the pharmacological properties of imeglimin, we here investigated the effects of imeglimin in hepatocytes and compared those with metformin. We investigated the genes expression in the cultured human hepatoma HepG2 cells by RNA-seq. HepG2 cells were stimulated with 0.25 mM, 3 mM metformin or imeglimin, or 1 mM AICAR, or vehicle alone for 12 h.
2022-08-01 | GSE208245 | GEO
Project description:Effects of imeglimin and metformin on islets of db/db mice
| PRJNA951370 | ENA
Project description:Imeglimin is a recently developed anti-diabetic drug that could concurrently promote insulin secretion and insulin sensitivity, while its mechanisms of action are not fully understood. Here we show that imeglimin administration could protect mice from high fat diet-induced weight gain with enhanced energy expenditure and attenuated whitening of brown adipose tissue. Imeglimin administration led to significant alteration of gut microbiota, which included an increase of Akkermansia genus, with attenuation of obesity-associated gut pathologies. Ablation of microbiota by antibiotic treatment partially abrogated the insulin sensitizing effects of imeglimin, while not affecting its actions on body weight gain or brown adipose tissue. Collectively, our results characterize imeglimin as a potential agent promoting energy expenditure and gut integrity, providing new insights into its mechanisms of action.
2024-02-16 | GSE255432 | GEO
Project description:Imeglimin is a first-in-class oral antidiabetic agent with reported mitochondrial and metabolic effects, but its direct actions on vascular smooth muscle cells remain incompletely understood. To explore transcriptomic changes associated with imeglimin exposure under mitogenic stimulation, rat aortic smooth muscle cells (RASMCs) were treated with imeglimin (2.5 mM) or vehicle from the time of seeding, serum-starved (0.2% FBS) for 48 h, and then switched to 10% FBS growth medium for 24 h while maintaining the same treatment. Total RNA was extracted and subjected to stranded mRNA sequencing. Sequencing was performed on an Illumina NovaSeq X Plus platform (paired-end 150 bp; ~6 Gb per sample). Reads were quality-checked, trimmed, aligned to the rat rn6 reference genome, and quantified at the gene level. Downstream analyses were performed to identify differentially expressed genes and enriched pathways. This dataset provides a resource to investigate imeglimin-associated transcriptional programs, including lipid/cholesterol metabolic pathways, in proliferative VSMC conditions.
2026-09-01 | GSE333627 | GEO
Project description: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.
2026-08-24 | GSE344280 | GEO
Project description:Abstract Background Sarcopenia is a major contributor to frailty and mortality in aging and obesity and is tightly linked to metabolic dysfunction. Imeglimin is a first-in-class oral hypoglycemic agent targeting mitochondrial function; however, despite the central role of mitochondria in skeletal muscle homeostasis, its effects on skeletal muscle under sarcopenia-relevant conditions remain unclear. Methods Imeglimin was administered to male C57BL/6 mice with high-fat diet (HFD)–induced obesity for six weeks and to naturally aged (18-month-old) male mice for 12 weeks. Skeletal muscle fiber morphology and transcriptomic profiles were analyzed in fast- and slow-twitch muscles. In parallel, C2C12 myotubes were exposed to palmitate with or without imeglimin, and inflammatory gene expression and reactive oxygen species (ROS) generation were assessed. Results Imeglimin significantly increased the cross-sectional area (CSA) of Type II fibers in the extensor digitorum longus (EDL) muscle of HFD-fed mice (+66%, P < 0.01 vs. controls). Transcriptomic analyses revealed suppression of conserved molecular signatures of muscle atrophy, including activation of immediate-early genes and inflammatory pathways (-62 to -79%, P < 0.05 vs. HFD-fed mice). In palmitate-treated C2C12 myotubes, imeglimin attenuated lipotoxicity-induced inflammatory gene expression (-28 to -72%, P < 0.05 vs. controls) with reduced ROS generation, consistent with its cell-autonomous effect on myocytes. Notably, in naturally aged mice, 12-week imeglimin treatment preserved EDL muscle fiber size (+14%, P < 0.05 vs. controls) without altering systemic glucose tolerance, accompanied by transcriptomic changes overlapping with those observed in the HFD model (-27 to -82%, P < 0.05 vs. aged controls). Conclusions Imeglimin attenuates skeletal muscle atrophy in obesity and aging, accompanied by coordinated suppression of stress- and inflammation-associated transcriptional programs. These findings indicate that pharmacological regulation of mitochondrial stress responses influences skeletal muscle vulnerability under chronic metabolic stress and identify skeletal muscle as a previously underappreciated target of imeglimin action.
2026-06-18 | GSE334796 | GEO