scholarly journals Comparative Evaluation of the Effect of Metformin and Insulin on Gut Microbiota and Metabolome Profiles of Type 2 Diabetic Rats Induced by the Combination of Streptozotocin and High-Fat Diet

2022 ◽  
Vol 12 ◽  
Author(s):  
Nan Hu ◽  
Qi Zhang ◽  
Hui Wang ◽  
Xuping Yang ◽  
Yan Jiang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Insulin Treatment ◽  
Serum Levels ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Therapeutic Effects ◽  
Metformin Treatment ◽  
High Fat

Lately, an increasing number of studies have investigated the relationship between metformin and gut microbiota, suggesting that metformin exerts part of its hypoglycemic effect through the microbes. However, its underlying mechanism remains largely undetermined. In the present study, we investigated the effects of metformin on gut microbiota and metabolome profiles in serum and compared it with insulin treatment in rats with type 2 diabetes mellitus (T2DM). Diabetic rats (DM group) were induced by a combination of streptozotocin and high-fat diet (HFD). After 7 days, DM rats were treated with metformin (MET group) or insulin (INS group) for 3 weeks. The 16S rRNA sequencing of the gut microbiota and non-targeted metabolomics analysis of serum were conducted. A total of 13 bile acids (BAs) in serum were further determined and compared among different groups. The rat model of T2DM was well established with the typical diabetic symptoms, showing significantly increased blood glucose, AUC of OGTT, HOMA-IR, TC, TG, LDL-C and TBA. Metformin or insulin treatment could ameliorate symptoms of diabetes and partly recover the abnormal biochemical indicators. Compared with DM rats, the relative abundances of 13 genera were significantly changed after metformin treatment, while only three genera were changed after insulin treatment. The metformin and insulin treatments also exhibited different serum metabolome profiles in T2DM rats. Moreover, 64 differential metabolites were identified between MET and DM groups, whereas 206 were identified between INS and DM groups. Insulin treatment showed greater influence on amino acids, glycerophospholipids/glycerolipids, and acylcarnitine compared with the metformin treatment, while metformin had an important impact on BAs. Furthermore, metformin could significantly decrease the serum levels of CA, GCA, UDCA, and GUDCA, but increase the level of TLCA in DM rats. Insulin treatment significantly decreased the levels of CA, UDCA, and CDCA. Besides, several metabolites in serum or microbiota were positively or negatively correlated with some bacteria. Collectively, our findings indicated that metformin had a stronger effect on gut microbiota than insulin, while insulin treatment showed greater influence on serum metabolites, which provided novel insights into the therapeutic effects of metformin on diabetes.

scholarly journals Dietary Polysaccharide from Enteromorpha clathrata Attenuates Obesity and Increases the Intestinal Abundance of Butyrate-producing Bacterium, Eubacterium xylanophilum, in Mice Fed a High-Fat Diet

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3286
Author(s):  
Jiali Wei ◽  
Yiran Zhao ◽  
Chen Zhou ◽  
Qing Zhao ◽  
Hongqian Zhong ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
High Throughput Sequencing ◽  
Serum Levels ◽  
Bioinformatic Analysis ◽  
The Body ◽  
Therapeutic Effects ◽  
High Fat ◽  
Intestinal Dysbiosis ◽  
Treatment Of Obesity

Previous studies have suggested that polysaccharide from Enteromorpha clathrata (ECP) could be used as a potential prebiotic to treat dysbiosis-associated diseases. However, whether it has any therapeutic effects on obesity has not been investigated. In the present study, we explored the anti-obesity effect of ECP and illustrated that it can significantly reduce the body weight and decrease the serum levels of triacylglycerol and cholesterol in high-fat diet (HFD)-fed mice. As revealed by 16S rRNA high-throughput sequencing and bioinformatic analysis, HFD remarkably changed the composition of the gut microbiota and promoted the growth of opportunistic pathogens such as Mucispirillum, Desulfobacterota and Alphaproteobacteria in obese mice. Interestingly, ECP improved intestinal dysbiosis caused by HFD and reshaped the structure of the gut microbiota in diseased mice by increasing the abundance of butyrate-producing bacterium, Eubacterium xylanophilum, in the gut. Altogether, we demonstrate for the first time an anti-obesity effect of ECP and shed new light into its therapeutic mechanisms from the perspective of gut microbiota. Our study will pave the way for the development of ECP as new prebiotic for the treatment of obesity and its associated disorders.

Effects of Ginkgo Biloba Extract on Liver Protection for Type 2 Diabetic Rats

2013 ◽  
Vol 790 ◽  
pp. 590-593
Author(s):  
Xu Sheng Li ◽  
Ren Yan Wu ◽  
Wei Ming Pan ◽  
Ye Hu
Keyword(s):  
Ginkgo Biloba ◽  
High Fat Diet ◽  
Serum Levels ◽  
Antioxidant Property ◽  
Ginkgo Biloba Extract ◽  
Diabetic Rats ◽  
High Fat ◽  
High Sucrose ◽  
Type 2 Diabetic

Type 2 diabetes was induced by feeding with high-sucrose-high-fat diet and injecting 25mg/kg streptozotocin. Rats were randomly divided into three groups: control, diabetic, diabetic simultaneously injected ip with Ginkgo biloba extract (EGb) for 8 wk. The treatment of EGb attenuated the development of hyperglycemia and hyperinsulinemia in type 2 diabetic rats. The serum levels of cholesterol, triglyceride as well as the activities of alanine aminotransferase, aspartate aminotransferase were significantly decreases in EGb-treated rats. The level of malondialdehyde were significantly increased in diabetic rats and decreased after EGb administration. Moreover, EGb markedly increased the activities of superoxide dismutase, catalase and glutathione peroxidase in liver. The results indicate that EGb has a protective effect on liver of type 2 diabetic rats, which may be related to decreases the accumulation of cholesterol, triglyceride in liver and its antioxidant property.

scholarly journals A Possible Mechanism of Metformin in Improving Insulin Resistance in Diabetic Rat Models

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Mengsiyu Li ◽  
Xiaowen Hu ◽  
Yeqiu Xu ◽  
Xiaolin Hu ◽  
Chunxue Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Diabetic Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Metformin Treatment ◽  
High Fat ◽  
Rat Models

Background. Type 2 diabetes has become one of the most common diseases worldwide, causing a serious social burden. As a first-line treatment for diabetes, metformin can effectively improve insulin resistance. It has been reported that 12α-hydroxylated BA (mainly CA) is associated with insulin resistance. The purpose of this study was to analyze the changes in CA and possible signaling mechanisms in diabetic rats after metformin intervention. Methods. HepG2 cells were cultured after adding different concentrations of metformin. The cell viability was measured using CCK8 kit, and the expression of FXR, MAFG, and CYP8B1 in cells was detected by WB. The rat models of type 2 diabetes were induced by low-dose streptozotocin by feeding a high-fat diet, and the control rats (CON) were fed on normal food; the diabetic rats (DM) were given a high-fat diet without supplementation with metformin, while the metformin-treated diabetic rats (DM + MET) were given a high-fat diet and supplemented with metformin. Biochemical parameters were detected at the end of the test. Expression levels of FXR, CYP8B1, and MAFG were assessed by WB. Serum CA were measured using an enzyme-linked immunosorbent assay (ELISA). Results. In HepG2 cells, metformin dose-dependently enhanced the transcriptional activity of FXR and MAFG and inhibited the expression of CYP8B1. Metformin-treated DM rats showed improved glucose and bile acid metabolism. In addition, significantly increased FXR and MAFG and decreased CYP8B1 were observed in DM + MET rats. At the same time, the CA content of metformin-treated rats was lower than that of diabetic rats. Conclusion. Changes in CA synthesis after metformin treatment may be associated with inhibition of CYP8B1. These results may play an important role in improving insulin sensitivity after metformin treatment.

Influance of regular swimming on serum levels of CRP, IL-6, TNF-α in high-fat diet-induced type 2 diabetic rats

2016 ◽  
Vol 35 (04) ◽  
pp. 469-476 ◽  
Author(s):  
Rafighe Ghiasi ◽  
Farhad Ghadiri Soufi ◽  
Gisou Mohaddes ◽  
Alireza Alihemmati ◽  
Mohammad H. Somi ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Serum Levels ◽  
Diabetic Rats ◽  
High Fat ◽  
Tnf Α ◽  
Type 2 Diabetic

Lactobacillus paracasei modulates the gut microbiota and improves inflammation in type 2 diabetic rats

2021 ◽  
Author(s):  
Zhu Zeng ◽  
Xiaoxuan Guo ◽  
Jinlan Zhang ◽  
Qipeng Yuan ◽  
Shangwu Chen
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Low Dose ◽  
Diabetic Rats ◽  
Lactobacillus Paracasei ◽  
High Fat ◽  
Probiotic Lactobacillus ◽  
Type 2 Diabetic

This study aimed to investigate the effects of probiotic Lactobacillus paracasei NL41 on inflammation and gut microbiota of type 2 diabetic (T2D) rats induced by high-fat diet (HFD) and low-dose...

scholarly journals Baicalin Attenuates High Fat Diet-Induced Obesity and Liver Dysfunction: Dose-Response and Potential Role of CaMKKβ/AMPK/ACC Pathway

2015 ◽  
Vol 35 (6) ◽  
pp. 2349-2359 ◽  
Author(s):  
Youli Xi ◽  
Miaozong Wu ◽  
Hongxia Li ◽  
Siqi Dong ◽  
Erfei Luo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Liver Steatosis ◽  
Serum Levels ◽  
Whole Body ◽  
Therapeutic Effects ◽  
High Fat ◽  
Dependent Protein

Background/Aims: Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms. Methods: High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated. Results: Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway. Conclusion: These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKβ/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.

scholarly journals The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Kira V. Derkach ◽  
Vera M. Bondareva ◽  
Oxana V. Chistyakova ◽  
Lev M. Berstein ◽  
Alexander O. Shpakov
Keyword(s):  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Low Dose ◽  
Diabetic Rats ◽  
Brain Serotonin ◽  
Serotonin Level ◽  
High Fat ◽  
Brain Serotonin Level ◽  
The Brain

In the last years the treatment of type 2 diabetes mellitus (DM2) was carried out using regulators of the brain signaling systems. In DM2 the level of the brain serotonin is reduced. So far, the effect of the increase of the brain serotonin level on DM2-induced metabolic and hormonal abnormalities has been studied scarcely. The present work was undertaken with the aim of filling this gap. DM2 was induced in male rats by 150-day high-fat diet and the treatment with low dose of streptozotocin (25 mg/kg) on the 70th day of experiment. From the 90th day, diabetic rats received for two months intranasal serotonin (IS) at a daily dose of 20 μg/rat. The IS treatment of diabetic rats decreased the body weight, and improved glucose tolerance, insulin-induced glucose utilization, and lipid metabolism. Besides, it restored hormonal regulation of adenylyl cyclase (AC) activity in the hypothalamus and normalized AC stimulation byβ-adrenergic agonists in the myocardium. In nondiabetic rats the same treatment induced metabolic and hormonal alterations, some of which were similar to those in DM2 but expressed to a lesser extent. In conclusion, the elevation of the brain serotonin level may be regarded as an effective approach to treat DM2 and its complications.

FPS-ZM1 Alleviates Circulating Indices of Liver Injury in Diet-Induced Type 2 Diabetic Mice

2022 ◽  
Author(s):  
Somayeh Aslani ◽  
Saman Bahrambeigi ◽  
Davoud Sanajou
Keyword(s):  
Liver Injury ◽  
High Fat Diet ◽  
Lifestyle Modification ◽  
Serum Levels ◽  
Diabetic Mice ◽  
High Fat ◽  
Lifestyle Modifications ◽  
Gamma Glutamyl Transpeptidase ◽  
Alcoholic Fatty Liver

Despite dietary/lifestyle modifications as well as glycemic and lipid control, non-alcoholic fatty liver disease (NAFLD) imposes a considerable risk to the patients by advancing to non-alcoholic steatohepatitis (NASH). The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor for advanced glycation end products (RAGE), against circulating indices of liver injury in high fat diet-induced diabetic mice. FPS-ZM1 at 0.5. 1, and 2 mg/kg (orally) was administered for 2 months, starting 4 months after provision of the high-fat diet. Tests for glucose homeostasis, liver injury markers, and hepatic/plasma miR-21 expressions were performed. FPS-ZM1 attenuated diabetes-induced elevations in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLD), and alpha glutathione-S-transferase (α-GST) as well as alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). It also decreased diabetes-associated elevations in serum ferritin and plasma cytokeratin 18 fragments. Additionally, FPS-ZM1 down-regulated elevated expressions of miR-21 in the liver and plasma of diabetic mice. These findings highlight the benefits of FPS-ZM in alleviating liver injury in mice evoked by high-fat diet-induced type 2 diabetes and suggest FPS-ZM1 as a new potential adjunct to the conventional diet/lifestyle modification and glycemic control in diabetics.

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