Effect of Astragalus Polysaccharide Combined with Metformin on Liver mRNA expression profile in aging type 2 diabetic mice and functional analysis
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ABSTRACT: Objective: To study the effect of astragalus polysaccharide combined with metformin on mRNA expression profile of type 2 diabetic mice, and to explore the molecular mechanism of astragalus polysaccharide combined with metformin in the treatment of type 2 aging diabetes. Methods: Natural aging mice were induced by high-sugar and high-fat diet combined with streptozotocin to prepare aging diabetes model. The experimental mice were divided into aging control group, aging diabetes model group, metformin treatment group, astragalus polysaccharide and metformin. The treatment group was treated with gavage for 60 consecutive days. Immunohistochemical detection of insulin levels in pancreatic tissue of each group of mice, serum insulin levels were measured by mouse insulin kit to observe the treatment of aging diabetes and astragalus polysaccharide combined with metformin; using Agilent mouse whole gene expression profile chip The mRNA expression changes of liver tissues in each group were analyzed, and the differential genes were screened by bioinformatics tools and the differential genes and signal pathways were enriched and analyzed. Results: Compared with the aging group, the insulin and insulin antibody levels in the model group were significantly decreased (P<0.05). Compared with the model group, the insulin and insulin antibody levels in the two treatment groups increased (P<0.05), and jaundice The level of polysaccharide in combination with metformin was significantly higher than that in metformin group (P<0.05). The differential gene analysis of the chip showed that there were 5617 differential genes in the aging diabetes model group, 3131 were up-regulated, and 2486 were down-regulated; the Astragalus polysaccharide combined with metformin treatment group had 4767 differential genes, compared with the aging diabetes model group. 2143 up-regulated, 2624 down-regulated, genes with significant differences were mainly involved in protease activity and drug metabolism, and significantly enriched into 33 signaling pathways (P<0.01). Conclusion: The gene regulatory network plays an important role in the intervention of Astragalus polysaccharides and metformin in the treatment of aging type 2 diabetes.
Project description:Objective: To study the effect of astragalus polysaccharide combined with metformin on mRNA expression profile of type 2 diabetic mice, and to explore the molecular mechanism of astragalus polysaccharide combined with metformin in the treatment of type 2 aging diabetes. Methods: Natural aging mice were induced by high-sugar and high-fat diet combined with streptozotocin to prepare aging diabetes model. The experimental mice were divided into aging control group, aging diabetes model group, metformin treatment group, astragalus polysaccharide and metformin. The treatment group was treated with gavage for 60 consecutive days. Immunohistochemical detection of insulin levels in pancreatic tissue of each group of mice, serum insulin levels were measured by mouse insulin kit to observe the treatment of aging diabetes and astragalus polysaccharide combined with metformin; using Agilent mouse whole gene expression profile chip The mRNA expression changes of liver tissues in each group were analyzed, and the differential genes were screened by bioinformatics tools and the differential genes and signal pathways were enriched and analyzed. Results: Compared with the aging group, the insulin and insulin antibody levels in the model group were significantly decreased (P<0.05). Compared with the model group, the insulin and insulin antibody levels in the two treatment groups increased (P<0.05), and jaundice The level of polysaccharide in combination with metformin was significantly higher than that in metformin group (P<0.05). The differential gene analysis of the chip showed that there were 5617 differential genes in the aging diabetes model group, 3131 were up-regulated, and 2486 were down-regulated; the Astragalus polysaccharide combined with metformin treatment group had 4767 differential genes, compared with the aging diabetes model group. 2143 up-regulated, 2624 down-regulated, genes with significant differences were mainly involved in protease activity and drug metabolism, and significantly enriched into 33 signaling pathways (P<0.01). Conclusion: The gene regulatory network plays an important role in the intervention of Astragalus polysaccharides and metformin in the treatment of aging type 2 diabetes.
Project description:Metformin is a medication that is commonly used in the treatment of diabetes. Recently small studies in cancer patients without diabetes suggest that metformin may benefit in lowering insulin levels. In those studies of patients with cancer but not diabetes, glucose (or sugar) levels in the blood are generally no lowered. Insulin and insulin-like growth factors affect the growth of cancer cells.
This randomized study will compare different interventions; exercise, exercise and metformin, metformin alone, or a control arm. The investigators are not directly testing how either exercise or metformin affects your disease. The investigators are testing how they affect insulin levels in your body as well as other blood markers. The investigators believe that these blood tests may either be related to cancer recurrences or be an early sign of cancer recurrences and they are testing how both exercise and metformin may change those markers.
Project description:Inflammation, oxidative and dicarbonyl stress play important roles in the pathophysiology of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver, however, its “pleiotropic“ effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP). In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL6 while levels of human CRP remained unchanged and metformin also significantly reduced oxidative stress (levels of conjugated dienes and TBARS) in the liver while no significant effects were observed in SHR control rats. In addition, in the presence of high human CRP, metformin reduced methylglyoxal levels in left ventricles but not in kidneys. Finally, metformin treatment reduced adipose tissue lipolysis. Possible molecular mechanisms of metformin action studied by gene expression profiling in the liver revealed deregulated genes from inflammatory, insulin signaling, AMP-activated protein kinase (AMPK) signaling and gluconeogenesis pathways. It can be concluded that in the presence of high levels of human CRP metformin protects against inflammation, oxidative and dicarbonyl stress in the heart and ameliorates insulin resistance and dyslipidemia.
Project description:Finally differentiated 3T3-L1 adipocytes are treated with insulin (0 or 100nM)or metformin (0 or 2mM)for 2 and 12 hours to understand insulin and metformin(an anti-diabetic drug commonly applied for Non-Insulin Dependent Diabetes Mellitus)action in adipose tissues.
Project description:The liver plays a critical role in avian reproduction as it is the primary site of de novo lipogenesis and yolk precursor synthesis. Broiler breeder hens, the parents of commercial broiler chickens, often experience poor reproductive efficiency primarily due to declining egg production beginning around 45 weeks of age. Metformin, an antidiabetic drug, exerts its primary effects in the liver by increasing insulin sensitivity and reducing hepatic glucose production in humans. This study aimed to characterize the liver transcriptomic profile of broiler breeder hens supplemented with metformin in the diet at 0 or 75 mg/kg body weight for 40 weeks (25-65 weeks of age; n=45 hens/treatment). Liver tissue was collected from a subset of hens (n=12 hens/treatment group) at 65 weeks of age, RNA was extracted and sequenced using next-generation sequencing. Differential gene abundance analysis revealed that metformin treatment led to the most significant changes in gene expression, with 552 genes differentially expressed compared to the control group. Further transcriptomic analysis highlighted increased expression of genes related to estrogen-stimulated yolk precursor synthesis, insulin-stimulated de novo lipogenesis, and AMPK-mediated glucose homeostasis. qPCR analysis revealed increased expression of ESR1, APOB, APOV1, VTG2, ADIPOQ, ADIPOR2 and ACACA mRNA and decreased expression of PCK1 mRNA validating the transcriptomic data. Collectively, the present study suggests that metformin supplementation supports prolonged egg production in aging broiler breeder hens by sustaining yolk precursor and fatty acid synthesis that are typically diminished in aging broiler breeder hens.
Project description:Metformin has been commonly used for decades to treat type 2 diabetes. Recent data indicates that mice treated with metformin live longer and healthier lives. Here, we show that chronic metformin exposure in mice and diabetics taking metformin have higher levels of the microRNA processing protein, Dicer. Examination of how metformin affects Dicer expression revealed that metformin alters binding of the AUF1 RNA-binding protein to DICER1 mRNA, which leads to stabilization of DICER1 mRNA. We found differential changes in microRNA expression in mice treated with metformin or caloric restriction, a proven life extending intervention. Several of these microRNAs are important for regulating cellular senescence and lifespan in model organisms. Consistent with this observation, treatment with metformin decreased cellular senescence in a Dicer-dependent manner. These data lead us to hypothesize that changes in Dicer levels may be important for organismal aging and that interventions that upregulate Dicer expression (e.g., metformin) may offer new therapeutic approaches to combat or prevent age-related diseases. Key words: diabetes mellitus, metformin, senescence, miRNA, RNA-binding proteins
Project description:We generated miRNA expression profiles of testes from breeder cocks fed with control diets and extra Astragalus Polysaccharide. A total of 663 and 660 miRNAs were expressed in control and APS groups, and there were 16 up-expressed miRNAs and 17 down-expressed miRNAs in APS group, compared with the control group meeting the criteria of P-values<0.05.
Project description:Metformin is the front-line treatment for type 2 diabetes worldwide. It acts via effects on glucose and lipid metabolism in metabolic tissues, leading to enhanced insulin sensitivity. Despite significant effort, the molecular basis for metformin response remains poorly understood, with a limited number of specific biochemical pathways studied to date. To broaden our understanding of hepatic metformin response, we combine phospho-protein enrichment in tissue from genetically engineered mice with a quantitative proteomics platform to enable the discovery and quantification of basophilic kinase substrates in-vivo. We define proteins that binding to 14-3-3 are acutely regulated by metformin treatment and/or loss of the serine/threonine kinase, LKB1. Inducible binding of 250 proteins following metformin treatment is observed, 44% LKB1-dependent. Beyond AMPK, metformin activates Protein Kinase D and MAPKAPK2 in an LKB1-independent manner, revealing additional kinases that may mediate aspects of metformin response. Deeper analysis uncovered substrates of AMPK in endocytosis and calcium homeostasis.
Project description:Effect of Astragalus Polysaccharide Combined with Metformin on Liver mRNA expression profile in aging type 2 diabetic mice and functional analysis
Project description:Effect of Astragalus Polysaccharide Combined with Metformin on Liver mRNA expression profile in aging type 2 diabetic mice and functional analysis