Project description:performing high-throughput RNA sequencing (RNA-Seq) transcriptomic analysis of hepatic cells after metformin or CWE treatment to identify changes in diabetes-related gene expression. Outcomes of this project provide evidence for the effectiveness of Ceylon cinnamon water extract compared to the current standard therapy for type 2 diabetes, metformin.
Project description:Metformin is the therapy of choice for treating type 2 diabetes and is currently repurposed for a wide range of diseases including aging. Recent evidence implicates the gut microbiota as a site of metformin action. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we performed C. elegans RNAseq to investigate the role of the metformin sensitive OP50 and metformin resistant OP50-MR E. coli microbiota in the drug effects on the host. Our data suggest an evolutionarily conserved bacterial mediation of metformin effects on host lipid metabolism and lifespan.
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.
Project description:Background: Metformin, one of the first-line medication for the treatment of type 2 diabetes and gestational diabetes, has recently be suggested for targeting cardiovascular disease, cancer and aging. Therefore, current understanding of the mechanism of this drug is incompletely understood, and the function of multiple tissues, other than liver metabolism alone, may be influenced. Methods: The wildtype healthy mice treated with metformin were compared with controls (treated with double distilled water). The transcriptome changes with/without metformin treatment were probed by using high-throughput RNA-seq techniques Results: A comprehensive mouse transcriptome map with metformin treatment across ten tissues including aorta, eyeball, brain, adipose tissue, heart, kidney, liver, skeletal muscle, stomach and testis, was provided. Function enrichment, network characteristics and disease association of the differentially expressed genes were analyzed. We also compared our expression profiles with related microarray data in order to find conditions that share similar expression profiles with metformin treatment. Conclusions: This dataset could serve as a baseline resource for investigating the potential beneficial or adverse effects of metformin across different tissues.
Project description:As our results suggested that metformin acts to limit mitochondrial ROS and calcium-mediated activation of IL-6, we reasoned it would likely affect other processes in alveolar macrophages triggered by exposure to particulate matter (PM). Therefore, we treated mice with metformin in the drinking water for 24 hours before we instilled PM intratracheally. We then flow-sorted alveolar macrophages from whole lung homogenates 24 hours later for transcriptomic analysis (RNA-Seq).
Project description:Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes. We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model. Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient (MCD) + high fat (HF) diet with or without 0.1% metformin for 8 weeks.
Project description:Reduced cancer incidence has been reported among type II diabetics treated with metformin. Metformin exhibits anti-proliferative and anti-neoplastic effects associated with inhibition of mTORC1, but the mechanisms are poorly understood. We provide the first genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) and metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Importantly, metformin's anti-proliferative activity can be explained by selective translational suppression of mRNAs encoding cell cycle regulators via the mTORC1/4E-BP pathway. Thus, metformin selectively inhibits mRNA translation of encoded proteins that promote neoplastic proliferation, motivating further studies of this compound and related biguanides in cancer prevention and treatment. MCF7 cells were treated with rapamycin, metformin or PP242 at concentrations that inhibited proliferation to 50% of control. Both cytoplasmic and polysome-associated mRNA was extracted from treatments and a vehicle treated control and probed with microarrays.
Project description:To test the effects of metformin on the human gut micorbiome, we fist collected human stool samples. We processed the samples in vitro culturing under anaerobic condition for 24 hours using the rapidAIM assay and either and cultured them with metformin, or DMSO as a control. We know that metformin can alter the human gut microbiome and were interested in better analyzing which functional proceses were altered.
Project description:The genome-wide transcriptional response of S. cerevisiae cells upon transfer to carbon-limited or carbon-limited and metformin supplemented media is investigated. DHO strain (BY4742 background) was cultivated batch-wise in SDC media at 30C and 180 rpm up to mid-exponential phase (OD600 ~ 0.6). The cells of the main culture were divided in three aliquots at the mid-exponential phase, centrifuged at 6000 rpm for 5 min, washed twice with deionized and distilled sterile water prior to their transfer to the treatment media. Treatment media comprised of SDC + 0.25% glucose for the C-lim control case and SDC +0.25%glucose + 1.66% metformin for the Met case. Control data for the reference condition (glucose limitation) is derived from E-MTAB-3001. Sample collection for transcriptional profiling was done at the 2nd hour of the transfer. The experiments were carried out in biological triplicates.