Similarities and Differences in the Intestinal Actions of Metformin and Imeglimin
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE304061 | GEO | 2025/09/01
REPOSITORIES: GEO
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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
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:Objective: To investigate the effects of metformin on intestinal carbohydrate metabolism in vivo.
Method: Male mice preconditioned with a high-fat, high-sucrose diet were treated orally with metformin or a control solution for two weeks. Fructose metabolism, glucose production from fructose, and production of other fructose-derived metabolites were assessed using stably labeled fructose as a tracer.
Results: Metformin treatment decreased intestinal glucose levels and reduced incorporation of fructose-derived metabolites into glucose. This was associated with decreased intestinal fructose metabolism as indicated by decreased enterocyte F1P levels and diminished labeling of fructose-derived metabolites. Metformin also reduced fructose delivery to the liver. Proteomic analysis revealed that metformin coordinately down-regulated proteins involved carbohydrate metabolism including those involved in fructolysis and glucose production within intestinal tissue.
Conclusion: Metformin reduces intestinal fructose metabolism, and this is associated with broad-based changes in intestinal enzyme and protein levels involved in sugar metabolism indicating that metformin's effects on sugar metabolism are pleiotropic.
2024-04-27 | PXD041833 | JPOST Repository
Project description:Metformin, a commonly used drug prescribed to treat type-2 diabetes, has been found to extend health span and delay cancer incidence and progression. Here, we report that starting chronic treatment with low dose of metformin (0.1% w/w in diet) at one year of age extends health and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with low dose metformin mimicked some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced LDL and cholesterol levels. At a molecular level, metformin increased AMP-activated protein kinase activity without attenuation of the mitochondrial electron transport chain activities. Metformin treatment resulted in lower chronic inflammation and increased antioxidant protection, suggesting that the ability of metformin to improve health of laboratory animals may stem from these factors. Our results support that metformin supplementation could be beneficial in extending health and lifespan in humans. Groups of one-year old male B6C57/J mice were maintained on ad libitum AIN-93G SD diet, or a 40% caloric restriction of the AIN-93G SD diet, or an ad libitum AIN-93G diet supplemented with 0.1% w/w metformin for the rest of their lives. 5 mice from each of these 3 groups were selected and RNA was extracted from both muscle and liver tissue using 1.0mm glass beads in a Precellys 24 Tissue Homogenizer and Qiagen RNeasy Mini Kits for Fibrous Tissue according to manufacturer's specifications. Quality and quantity of the total RNA was checked with the Agilent 2100 bioanalyzer using RNA 6000 Nano chips. RNA samples were labeled using the Illumina TotalPrep RNA Amplification Kit. In short, 0.5g of total RNA was first converted into single-stranded cDNA with reverse transcriptase using an oligo-dT primer containing the T7 RNA polymerase promoter site and then copied to produce double-stranded cDNA molecules. The double stranded cDNA was cleaned and concentrated with the supplied columns and used in an overnight in-vitro transcription reaction where single-stranded RNA (cRNA) was generated and labeled by incorporation of biotin-16-UTP. Arrays were hybridized using a total of 0.75ug of biotin-labeled cRNA at 58 degrees C for 16 hours to Illumina's Sentrix MouseRef-8 v2 Expression BeadChips. Each BeadChip has ~24,000 well-annotated RefSeq transcripts with approximately 30-fold redundancy. The arrays were washed, blocked and the biotin labeled cRNA was detected by staining with streptavidin-Cy3. Arrays were scanned at a resolution of 0.8um using the Beadstation 500 X from Illumina and the data was extracted using the Illumina GenomeStudio software(v1.6.0). Any spots at or below the background were filtered out using an Illumina detection p value of 0.02 and above. The natural log of all remaining scores were used to find the avg and std of each array and the z-score normalization was calculated and presented below. Z-score = (raw value - avg)/std.
2013-07-31 | E-GEOD-40936 | biostudies-arrayexpress
Project description:Chronic kidney disease (CKD) is one of the major global health problems with high incidence, poor prognosis and high medical cost. However, few pharmacological options are available for CKD. Metformin is widely used for treatment of type-2 diabetes, but recent works showed that metformin ameliorates tumor progression, inflammatory disease and tissue fibrosis. Whether metformin ameliorates non-diabetic chronic glomerular disease and CKD is unexplored. Here we showed that metformin or losartan (used as control) has protective effects against CKD by suppressing proteinuria, renal inflammation, fibrosis and glomerular injury in Alport syndrome mouse model, which spontaneously manifests chronic glomerular and kidney disease. Transcriptome analysis showed that metformin and losartan influenced molecular pathways of metabolism and inflammation, respectively. While metformin specifically affected genes that were classified as metabolic regulators, losartan specifically altered genes that were classified as inflammatory regulators. Metformin also induced multiple signaling pathways not affected by losartan. Overall, metformin ameliorates non-diabetic chronic glomerular diseases, and could be considered a therapeutic option for CKD. We used microarrays to investigate the global gene expression underlying the protective effects of metformin on Alport syndrome mice model
2021-01-30 | GSE109861 | GEO
Project description:Metformin, a commonly used drug prescribed to treat type-2 diabetes, has been found to extend health span and delay cancer incidence and progression. Here, we report that starting chronic treatment with low dose of metformin (0.1% w/w in diet) at one year of age extends health and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with low dose metformin mimicked some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced LDL and cholesterol levels. At a molecular level, metformin increased AMP-activated protein kinase activity without attenuation of the mitochondrial electron transport chain activities. Metformin treatment resulted in lower chronic inflammation and increased antioxidant protection, suggesting that the ability of metformin to improve health of laboratory animals may stem from these factors. Our results support that metformin supplementation could be beneficial in extending health and lifespan in humans.
2013-07-31 | GSE40936 | GEO
Project description:Metformin is a commonly used antihyperglycaemic agent for the treatment of type 2 diabetes. Nevertheless, the exact mechanisms of action, underlying the various therapeutic effects of metformin, remain elusive. The goal of this study was to evaluate the alterations in longitudinal whole-blood transcriptome profiles of healthy individuals after a one-week metformin intervention in order to identify the novel molecular targets and further prompt the discovery of predictive biomarkers of metformin response. Next generation sequencing-based transcriptome analysis revealed four clusters of functionally related genes with a subject-specific differential expression even after a single dose of metformin: ribosomal genes and their pseudogenes (e.g., RNA5-8SN1, RNA5-8SN5, RNY4P10), small nuclear RNAs (e.g., SNORA20, SCARNA5, SNORA80E), genes relevant to insulin production (HNF1B, HNF1A, HNF4A, GCK, INS, NEUROD1, PAX4, PDX1, ABCC8, KCNJ11) and cholesterol homeostasis (APOB, LDLR, PCSK9). After accounting for subject-specific expression, the enrichment of pathways associated with immune responses, such as intestinal immune network for IgA production and cytokine-cytokine receptor interaction were observed for the majority of the cohort. The results of the study reveal for the first time a strong inter-individual variation of the metformin effect on the transcriptional regulation, that goes in line with well-known variability of the therapeutic response to the drug.
2019-09-13 | GSE137317 | GEO