scholarly journals Analysis of the physiological mechanisms underlying the biological activity of sargassum fusiforme fucoidan to alleviate insulin resistance

2021 ◽  
Author(s):  
◽  
Ya Zhang
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Signaling Pathway ◽  
High Fat Diet ◽  
High Fat ◽  
Physiological Mechanisms ◽  
Ceramide Level ◽  
Sargassum Fusiforme

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia resulting from progressive loss of β-cell insulin secretion frequently on the background of insulin resistance. T2DM, also known as non-insulin-dependent diabetes, accounts for more than 90% of all cases of diabetes. Insulin resistance (IR) refers to the reduced sensitivity of peripheral tissues to insulin and is one of the important triggers of type 2 diabetes. Sargassum fusiforme polysaccharide exhibits diverse biological activities, and more and more studies have shown it has a significant effect in improving insulin resistance with almost no side effects. Sargassum fusiforme fucoidan (SFF) is one of the main active components with active ingredients such as antioxidants and hypoglycemic lipids. However, the ameliorative effects of SFF on high-fat diet-induced insulin resistance mice and its underlying physiological mechanisms are not clear. Hence, the polysaccharides were extracted and purified from Sargassum fusiforme, and fucoidan (SFF), which has good antioxidant activity, was screened using a drosophila melanogaster aging model. The effect of SFF on the amelioration of insulin resistance in mice was investigated with a high-fat obese insulin resistance mice model. By gut microbiota and metabolomics techniques, the effect of SFF on intestinal metabolites and its mechanism of alleviate IR were investigated. After treatment with 200 mg/kg SFF for 8 weeks, it was found that SFF could reduce body weight, fasting blood glucose and homa-IR in insulin resistance mice. SFF could effectively activate Nrf2/ARE antioxidant signaling pathway in the liver and promote Nrf2 entry into the nucleus and downstream gene transcription. Metabolomics and intestinal microecology revealed that SFF could upregulate TUDCA level and downregulate ceramide level in mice colon and serum, and this change was dependent on gut microbiota. TUDCA effectively inhibits the FXR/SHP signaling pathway activated by a high-fat diet, thereby reducing the biosynthesis of enteric-derived ceramides. In addition, TUDCA in the liver could compete with Nrf2 to bind Keap1 to reduce the formation of the Nrf2/Keap1 complex, reduce Nrf2 ubiquitination, and thus contribute to Nrf2/ARE signaling activation. In conclusion, fucoidan from S. fusiforme was able to modulate gut microbiota, increased the levels of the intestinal metabolite TUDCA, reduced biosynthesis of entericderived ceramides and activated the Nrf2/ARE pathway, which in turn significantly improved insulin resistance induced by high-fat diet in mice. This study provides a new research idea for the study of brown algae fucoidan in metabolic diseases.

Abstract 015: Increased 20-HETE Levels Contribute to Impaired Glucose Metabolism and Type 2 Diabetes in Cyp4a14 Knockout Mice Fed on High Fat Diet.

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Varunkumar G Pandey ◽  
Lars Bellner ◽  
Victor Garcia ◽  
Joseph Schragenheim ◽  
Andrew Cohen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Weight Gain ◽  
Blood Glucose ◽  
High Fat Diet ◽  
Plasma Insulin ◽  
High Fat ◽  
Plasma Insulin Levels

20-HETE (20-Hydroxyeicosatetraenoic acid) is a cytochrome P450 ω-hydroxylase metabolite of arachidonic acid that promotes endothelial dysfunction, microvascular remodeling and hypertension. Previous studies have shown that urinary 20-HETE levels correlate with BMI and plasma insulin levels. However, there is no direct evidence for the role of 20-HETE in the regulation of glucose metabolism, obesity and type 2 diabetes mellitus. In this study we examined the effect of 20-SOLA (2,5,8,11,14,17-hexaoxanonadecan-19-yl-20-hydroxyeicosa-6(Z),15(Z)-dienoate), a water-soluble 20-HETE antagonist, on blood pressure, weight gain and blood glucose in Cyp4a14 knockout (Cyp4a14-/-) mice fed high-fat diet (HFD). The Cyp4a14-/- male mice exhibit high vascular 20-HETE levels and display 20-HETE-dependent hypertension. There was no difference in weight gain and fasting blood glucose between Cyp4a14-/- and wild type (WT) on regular chow. When subjected to HFD for 15 weeks, a significant increase in weight was observed in Cyp4a14-/- as compared to WT mice (56.5±3.45 vs. 30.2±0.7g, p<0.05). Administration of 20-SOLA (10mg/kg/day in drinking water) significantly attenuated the weight gain (28.7±1.47g, p<0.05) and normalized blood pressure in Cyp4a14-/- mice on HFD (116±0.3 vs. 172.7±4.6mmHg, p<0.05). HFD fed Cyp4a14-/- mice exhibited hyperglycemia as opposed to normal glucose levels in WT on a HFD (154±1.9 vs. 96.3±3.0 mg/dL, p<0.05). 20-SOLA prevented the HFD-induced hyperglycemia in Cyp4a14-/- mice (91±8mg/dL, p<0.05). Plasma insulin levels were markedly high in Cyp4a14-/- mice vs. WT on HFD (2.66±0.7 vs. 0.58±0.18ng/mL, p<0.05); corrected by the treatment with 20-SOLA (0.69±0.09 ng/mL, p<0.05). Importantly, glucose and insulin tolerance tests showed impaired glucose homeostasis and insulin resistance in Cyp4a14-/- mice on HFD; ameliorated by treatment with 20-SOLA. This novel finding that blockade of 20-HETE actions by 20-SOLA prevents HFD-induced obesity and restores glucose homeostasis in Cyp4a14-/- mice suggests that 20-HETE contributes to obesity, hyperglycemia and insulin resistance in HFD induced metabolic disorder. The molecular mechanisms underlying 20-HETE mediated metabolic dysfunction are being currently explored.

Lactobacillus acidophilus alleviates type 2 diabetes by regulating hepatic glucose, lipid metabolism and gut microbiota in mice

2019 ◽  
Vol 10 (9) ◽  
pp. 5804-5815 ◽  
Author(s):  
Fenfen Yan ◽  
Na Li ◽  
Jialu Shi ◽  
Huizhen Li ◽  
Yingxue Yue ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Lactobacillus Acidophilus ◽  
High Fat Diet ◽  
High Fat ◽  
Glucose And Lipid Metabolism ◽  
Hepatic Glucose

Lactobacillus acidophilus alleviates type 2 diabetes induced by a high fat diet and streptozotocin (STZ) injection by regulating gut microbiota, hepatic glucose and lipid metabolism in mice.

scholarly journals Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

2020 ◽  
Vol 295 (31) ◽  
pp. 10842-10856 ◽  
Author(s):  
Wen Liu ◽  
Ye Yin ◽  
Meijing Wang ◽  
Ting Fan ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Low Grade ◽  
High Fat ◽  
Caspase 1

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro. Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.

scholarly journals Establishment of long-term high-fat diet and low dose streptozotocin-induced experimental type-2 diabetes mellitus model of insulin resistance and evaluation of seed extracts of Syzygium cumini

2021 ◽  
Vol 10 (3) ◽  
pp. 331-338
Author(s):  
Pratibha Nadig ◽  
Meharban Asanaliyar ◽  
Kevin Manohar Salis
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Low Dose ◽  
Syzygium Cumini ◽  
High Fat ◽  
Glut 4 ◽  
Seed Extracts

Introduction: The principal mechanism responsible for reducing blood glucose is through insulin-stimulated glucose transport into skeletal muscle. The transporter protein that mediates this uptake is GLUT-4. A defect in this step is associated with reduced glucose utilization in muscle and adipose tissue, as observed in insulin-resistant type-2 diabetes mellitus (T2DM) patients. This study aimed to develop an experimental T2DM model and evaluate altered glucose transporter type 4 (GLUT-4) levels as a biomarker of insulin resistance. Antidiabetic activities of Syzygium cumini hydro-ethanolic seed extracts (SCE) were also evaluated. Methods: Adult male Wistar albino rats were fed a high-fat diet for 12 weeks and dosed intraperitoneally with streptozotocin (35 mg/kg). After treatment for 21 days, all investigations were done. The homeostasis model of assessment (HOMA) was used for the calculation of insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) index. Diaphragm muscle and retroperitoneal fat were collected for real-time polymerase chain reaction (RT-PCR) studies. Results: A significant increase in fasting blood glucose, HOMA-IR, and serum lipids, and a decrease in serum insulin and HOMA-B were observed in the diabetic group, effects that reversed following pioglitazone and SCE treatment. The diabetic group showed a downregulation of GLUT-4 expression in skeletal muscle while an increase was observed in adipose tissue. Conclusion: A high-fat diet and low dose streptozotocin-induced experimental T2DM model of insulin resistance was developed to screen novel insulin sensitizers. Data generated demonstrated that altered GLUT-4 levels could be used as a biomarker of insulin resistance. Antidiabetic activity of S. cumini hydro-ethanolic seed extract was also confirmed in this study.

Ginsenoside Rk3 ameliorates high-fat-diet/streptozocin induced type 2 diabetes mellitus in mice via the AMPK/Akt signaling pathway

2019 ◽  
Vol 10 (5) ◽  
pp. 2538-2551 ◽  
Author(s):  
Yao Liu ◽  
Jianjun Deng ◽  
Daidi Fan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Active Ingredient ◽  
High Fat Diet ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
High Fat

Ginsenoside Rk3 (G-Rk3) is a main active ingredient of ginsenosides.

Probiotic-fermented blueberry juice prevents obesity and hyperglycemia in high fat diet-fed mice in association with modulating the gut microbiota

2020 ◽  
Vol 11 (10) ◽  
pp. 9192-9207
Author(s):  
Hao Zhong ◽  
Abdullah ◽  
Lingli Deng ◽  
Minjie Zhao ◽  
Jun Tang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
High Fat ◽  
Blueberry Juice

Fermented blueberry juice intervention has demonstrated remarkable potential against obesity and type 2 diabetes mellitus.

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