scholarly journals Antidiabetic Effect of Casein Glycomacropeptide Hydrolysates on High-Fat Diet and STZ-Induced Diabetic Mice via Regulating Insulin Signaling in Skeletal Muscle and Modulating Gut Microbiota

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 220 ◽  
Author(s):  
Qichen Yuan ◽  
Biyuan Zhan ◽  
Rui Chang ◽  
Min Du ◽  
Xueying Mao
Keyword(s):  
Skeletal Muscle ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Glucose Transporter ◽  
Glycogen Synthase ◽  
Fasting Blood Glucose ◽  
Diabetic Mice ◽  
High Fat ◽  
Antidiabetic Effect ◽  
Glucose Levels

This study evaluated the effects and the underlying mechanisms of casein glycomacropeptide hydrolysate (GHP) on high-fat diet-fed and streptozotocin-induced type 2 diabetes (T2D) in C57BL/6J mice. Results showed that 8-week GHP supplementation significantly decreased fasting blood glucose levels, restored insulin production, improved glucose tolerance and insulin tolerance, and alleviated dyslipidemia in T2D mice. In addition, GHP supplementation reduced the concentration of lipopolysaccharides (LPSs) and pro-inflammatory cytokines in serum, which led to reduced systematic inflammation. Furthermore, GHP supplementation increased muscle glycogen content in diabetic mice, which was probably due to the regulation of glycogen synthase kinase 3 beta and glycogen synthase. GHP regulated the insulin receptor substrate-1/phosphatidylinositol 3-kinase/protein kinase B pathway in skeletal muscle, which promoted glucose transporter 4 (GLUT4) translocation. Moreover, GHP modulated the overall structure and diversity of gut microbiota in T2D mice. GHP increased the Bacteroidetes/Firmicutes ratio and the abundance of S24-7, Ruminiclostridium, Blautia and Allobaculum, which might contribute to its antidiabetic effect. Taken together, our findings demonstrate that the antidiabetic effect of GHP may be associated with the recovery of skeletal muscle insulin sensitivity and the regulation of gut microbiota.

Intake of Flavonoids from Astragalus Membranaceus Ameliorated Brain Impairment in Diabetic Mice Via Modulating Brain-Gut Axis

2021 ◽  
Author(s):  
Li Xuling ◽  
Junling Gu ◽  
Zhe Wang ◽  
Jing Lin ◽  
Tingting Zhao ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Brain Damage ◽  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Synaptic Function ◽  
Astragalus Membranaceus ◽  
Immunological Methods ◽  
Diabetic Mice ◽  
High Fat

Abstract Background: Brain impairment is one of a major complication of diabetes. Dietary flavonoids have been recommended to prevent brain damage. Astragalus membranaceus is a herbal medicine commonly used to relieve the complications of diabetes. Flavonoids is one of the major ingredients of Astragalus membranaceus, but its function and mechanism on diabetic encepholopathy is still unknown.Methods: Type 2 diabetes mellitus (T2DM) model was induced by high fat diet and STZ in C57BL/6J mice, and BEnd.3 and HT22 cell lines were applied in the in vitro study. Quality of flavonoids was evaluated by LC-MS/MS. Differential expressed proteins in the hippocampus were evaluated by proteomics; influence of the flavonoids on composition of gut microbiota was analyzed by metagenomics. Mechanism of the flavonoids on diabetic encepholopathy was analyzed by Q-PCR, Western Blot, and multi-immunological methods et al. Results: We found that flavonoids from Astragalus membranaceus (TFA) significantly ameliorated brain damage by modulating gut-microbiota-brain axis: TFA oral administration decreased fasting blood glucose and food intake, repaired blood brain barrier, protected hippocampus synaptic function; improved hippocampus mitochondrial biosynthesis and energy metabolism; and enriched the intestinal microbiome in high fat diet/STZ-induced diabetic mice. In the in vitro study, we found TFA increased viability of HT22 cells and preserved gut barrier integrity in CaCO2 monocellular layer, and PGC1α/AMPK pathway participated in this process. Conclusion: Our findings demonstrated that flavonoids from Astragalus Membranaceus ameliorated brain impairment via gut-brain axis. Our present study provided an alternative solution on preventing and treating diabetic cognition impairment.

scholarly journals Antidiabetic Effect of Tibetan Medicine Tang-Kang-Fu-San on High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Bailu Duan ◽  
Zhongqiu Zhao ◽  
Ling Lin ◽  
Jing Jin ◽  
Lijun Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
Glucose Transporter ◽  
Fasting Blood Glucose ◽  
Tibetan Medicine ◽  
Chemical Compositions ◽  
High Fat ◽  
Hplc Fingerprint ◽  
Underlying Mechanisms

The aim of this study was to investigate the antidiabetic effects of a Tibetan medicine, Tang-Kang-Fu-San (TKFS), on experimental type 2 diabetes mellitus (T2DM) rats and to explore its underlying mechanisms. Firstly two major chemical compositions of TKFS, gallic acid and curcumin, were characterized by HPLC fingerprint analysis. Next T2DM in rats was induced by high-fat diet and a low-dose streptozotocin (STZ 35 mg/kg). Then oral gavage administration of three different doses of TKFS (0.3 g/kg, 0.6 g/kg, and 1.2 g/kg) was given to T2DM rats. Experimental results showed that TKFS dramatically reduced the levels of fasting blood glucose, fasting blood insulin, triglyceride, total cholesterol, LDL cholesterol, and HDL cholesterol, even though it did not alter the animal body weight. The downregulation of phosphorylation-AKT (p-AKT) and glucose transporter-4 (GLUT4) in skeletal muscle of T2DM rats was restored and abnormal pathological changes in pancreas tissues were also improved. Our work showed that TKFS could alleviate diabetic syndromes, maintain the glucose homeostasis, and protect against insulin resistance in T2DM rats, and the improvement of AKT phosphorylation and GLUT4 translocation in skeletal muscle would be one of its possible underlying mechanisms.

scholarly journals Beneficial Effects of Potentilla discolor Bunge Water Extract on Inflammatory Cytokines Release and Gut Microbiota in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 670 ◽  
Author(s):  
Lihua Han ◽  
Tiange Li ◽  
Min Du ◽  
Rui Chang ◽  
Biyuan Zhan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Intestinal Inflammation ◽  
Water Extract ◽  
Perennial Herb ◽  
Diabetic Mice ◽  
High Fat ◽  
Type 2 Diabetic

Potentilla discolor Bunge (PDB), a perennial herb, has been used as a traditional Chinese medicine in the therapy of many diseases. The aim of the current study was to investigate the effect of PDB water extract on systemic inflammation and gut microbiota in type 2 diabetic (T2D) mice induced by high-fat diet (HFD) and streptozotocin (STZ) injection. C57BL/6J mice were randomly divided into a normal diet (ND) group, T2D group, and PDB group (diabetic mice treated with PDB water extract at a dose of 400 mg/kg body weight). Results showed that PDB significantly decreased the levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines in serum. Further investigation showed that PDB significantly reduced the ratio of Firmicutes/Bacteroidetes and the relative abundance of Proteobacteria in fecal samples of diabetic mice. In addition, PDB notably alleviated intestinal inflammation as evidenced by decreased expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-κB (NF-κB), and inflammatory cytokines. PDB also reversed the decreased expression of intestinal mucosal tight junction proteins including Claudin3, ZO-1, and Occludin. Meanwhile, the levels of fecal acetic acid and butyric acid and their specific receptors including G-protein-coupled receptor (GPR) 41 and 43 expression in the colon were also increased after PDB treatment. Our results indicated that PDB might serve as a potential functional ingredient against diabetes and related inflammation.

scholarly journals Alisporivir Treatment Alleviates Mitochondrial Dysfunction in the Skeletal Muscles of C57BL/6NCrl Mice with High-Fat Diet/Streptozotocin-Induced Diabetes Mellitus

2021 ◽  
Vol 22 (17) ◽  
pp. 9524
Author(s):  
Konstantin N. Belosludtsev ◽  
Vlada S. Starinets ◽  
Eugeny Yu. Talanov ◽  
Irina B. Mikheeva ◽  
Mikhail V. Dubinin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
Skeletal Muscles ◽  
Diabetic Mice ◽  
High Fat ◽  
Muscle Mitochondria ◽  
Skeletal Muscle Mitochondria ◽  
Pore Opening

Diabetes mellitus is a systemic metabolic disorder associated with mitochondrial dysfunction, with mitochondrial permeability transition (MPT) pore opening being recognized as one of its pathogenic mechanisms. Alisporivir has been recently identified as a non-immunosuppressive analogue of the MPT pore blocker cyclosporin A and has broad therapeutic potential. The purpose of the present work was to study the effect of alisporivir (2.5 mg/kg/day i.p.) on the ultrastructure and functions of the skeletal muscle mitochondria of mice with diabetes mellitus induced by a high-fat diet combined with streptozotocin injections. The glucose tolerance tests indicated that alisporivir increased the rate of glucose utilization in diabetic mice. An electron microscopy analysis showed that alisporivir prevented diabetes-induced changes in the ultrastructure and content of the mitochondria in myocytes. In diabetes, the ADP-stimulated respiration, respiratory control, and ADP/O ratios and the level of ATP synthase in the mitochondria decreased, whereas alisporivir treatment restored these indicators. Alisporivir eliminated diabetes-induced increases in mitochondrial lipid peroxidation products. Diabetic mice showed decreased mRNA levels of Atp5f1a, Ant1, and Ppif and increased levels of Ant2 in the skeletal muscles. The skeletal muscle mitochondria of diabetic animals were sensitized to the MPT pore opening. Alisporivir normalized the expression level of Ant2 and mitochondrial susceptibility to the MPT pore opening. In parallel, the levels of Mfn2 and Drp1 also returned to control values, suggesting a normalization of mitochondrial dynamics. These findings suggest that the targeting of the MPT pore opening by alisporivir is a therapeutic approach to prevent the development of mitochondrial dysfunction and associated oxidative stress in the skeletal muscles in diabetes.

scholarly journals Glucosamine Ameliorates Symptoms of High-Fat Diet-Fed Mice by Reversing Imbalanced Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Xubing Yuan ◽  
Junping Zheng ◽  
Lishi Ren ◽  
Siming Jiao ◽  
Cui Feng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Inflammatory Responses ◽  
Fasting Blood Glucose ◽  
Intestinal Barrier ◽  
Intestinal Bacteria ◽  
High Fat ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Rdna Sequencing

Glucosamine (GlcN) is used as a supplement for arthritis and joint pain and has been proved to have effects on inflammation, cancer, and cardiovascular diseases. However, there are limited studies on the regulatory mechanism of GlcN against glucose and lipid metabolism disorder. In this study, we treated high-fat diet (HFD)-induced diabetic mice with GlcN (1 mg/ml, in drinking water) for five months. The results show that GlcN significantly reduced the fasting blood glucose of HFD-fed mice and improved glucose tolerance. The feces of intestinal contents in mice were analyzed using 16s rDNA sequencing. It was indicated that GlcN reversed the imbalanced gut microbiota in HFD-fed mice. Based on the PICRUSt assay, the signaling pathways of glucolipid metabolism and biosynthesis were changed in mice with HFD feeding. By quantitative real-time PCR (qPCR) and hematoxylin and eosin (H&E) staining, it was demonstrated that GlcN not only inhibited the inflammatory responses of colon and white adipose tissues, but also improved the intestinal barrier damage of HFD-fed mice. Finally, the correlation analysis suggests the most significantly changed intestinal bacteria were positively or negatively related to the occurrence of inflammation in the colon and fat tissues of HFD-fed mice. In summary, our studies provide a theoretical basis for the potential application of GlcN to glucolipid metabolism disorder through the regulation of gut microbiota.

scholarly journals Effect of Dietary Silk Peptide on Obesity, Hyperglycemia, and Skeletal Muscle Regeneration in High-Fat Diet-Fed Mice

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 377 ◽  
Author(s):  
Kippeum Lee ◽  
Heegu Jin ◽  
Sungwoo Chei ◽  
Hyun-Ji Oh ◽  
Jeong-Yong Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Fat Diet ◽  
Glucose Transporter ◽  
Uncoupling Protein ◽  
Skeletal Muscle Regeneration ◽  
High Fat ◽  
Skeletal Muscle Function ◽  
Silk Peptide

Obesity is associated with excess body fat accumulation that can cause hyperglycemia and reduce skeletal muscle function and strength, which characterize the development of sarcopenic obesity. In this study, we aimed to determine the mechanism whereby acid-hydrolyzed silk peptide (SP) prevents high-fat diet (HFD)-induced obesity and whether it regulates glucose uptake and muscle differentiation using in vivo and in vitro approaches. Our findings demonstrate that SP inhibits body mass gain and the expression of adipogenic transcription factors in visceral adipose tissue (VAT). SP also had an anti-diabetic effect in VAT and skeletal muscle because it upregulated glucose transporter type 4 (GLUT4) and uncoupling protein 3 (UCP3) expression. Furthermore, SP reduced ubiquitin proteasome and promoted myoblast determination protein 1 (MyoD)/myogenic factor 4 (myogenin) expression, implying that it may have potential for the treatment of obesity-induced hyperglycemia and obesity-associated sarcopenia.

Punicalagin alleviates renal injury via the gut-kidney axis in high-fat diet-induced diabetic mice

2022 ◽  
Author(s):  
Qinglian Hua ◽  
Ya Ling Han ◽  
Haifeng Zhao ◽  
Haowen Zhang ◽  
Bei Yan ◽  
...  
Keyword(s):  
Renal Function ◽  
Gut Microbiota ◽  
Renal Injury ◽  
High Fat Diet ◽  
Intestinal Barrier ◽  
Diabetic Mice ◽  
High Fat ◽  
Microbial Ecosystem

Diabetic renal injury was associated with dysbiosis of the gut microbiota and intestinal barrier. Punicalagin (PU) from pomegranates potentially impacts the microbial ecosystem, intestinal barrier, and renal function. Therefore, we...

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