The alterations of bile acids in rats with high-fat diet/streptozotocin-induced type 2 diabetes and their negative effects on glucose metabolism

Zhang, Fan; Wang, Yuan; Wei, Yuhui; Zhang, Dongmei; Duan, Yingting; Li, Boxia; Wang, Xiaohui; Xi, Lili; Zhou, Yan; Wu, Xinan

doi:10.1016/j.lfs.2019.05.031

Cited by 26 publications

(15 citation statements)

References 45 publications

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“…In the present study, to mimic the progression of T2DM in humans, rat models of T2DM induced by a high-fat diet followed by low-dose STZ injection were generated. Compared with the rats with spontaneous diabetes, model animals such as those used in the present study are readily available, are more cost effective and therefore have been used for evaluating drug efficacy for T2DM (19,20). In the present study, compared with the HF control group, the model group exhibited significantly increased fasting blood glucose levels and insulin resistance, though no significant difference was observed in fasting serum insulin levels.…”

Section: Discussionmentioning

confidence: 65%

Molecular hydrogen improves type 2 diabetes through inhibiting oxidative stress

Han

et al. 2020

Exp Ther Med

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The aim of the present study was to investigate the potential therapeutic effects of molecular hydrogen on type 2 diabetes mellitus (T2DM) in rats. Following maintenance on a high-fat diet for 4 weeks, a T2DM model was established using an injection of 30 mg/kg streptozotocin via the caudal vein into Sprague-Dawley rats. On day 0 and Day 80, the blood samples were obtained from each rat for the measurement of biochemical indicators including blood lipids, fasting blood glucose, hepatic glycogen, fasting serum insulin, insulin sensitivity index, insulin resistance index, serum superoxide dismutase (SOD) and serum malondialdehyde (MDA) using an automatic biochemical analyzer. The kidneys and pancreas tissues were harvested for HE staining and Western blot assay of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated (p)-p65, p65, p-IκB and IκB. The results showed that in rats with T2DM, molecular hydrogen treatment decreased fasting blood glucose levels, increased hepatic glycogen synthesis and improved insulin sensitivity. Treatment with molecular hydrogen also increased the production of SOD whilst decreasing the production of MDA. In addition, molecular hydrogen alleviated the pathological changes exhibited by pancreatic islets and kidney during T2DM. Mechanistically, molecular hydrogen decreased TLR4 and MyD88 expression levels whilst also decreasing p65 and NF-κB inhibitor phosphorylation. In conclusion, molecular hydrogen exerted therapeutic effects against T2DM by improving hyperglycemia and inhibiting oxidative stress through mechanisms that are associated with the TLR4/MyD88/NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 65%

Molecular hydrogen improves type 2 diabetes through inhibiting oxidative stress

Han

et al. 2020

Exp Ther Med

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“…Hence, a sucrose rich diet could accelerate the development of metabolic syndrome and cause fatty liver disease. In addition, it may induce pancreatic inflammation with increased macrophage infiltration, which might reduce insulin secretion [61] and consequently blood glucose parameters' deterioration. Similarly, diets containing only fructose and glucose showed worsened diabetes condition in 67% of the studies and the other 33% showed no difference.…”

Section: Sucrose Fructose Glucose and High Glycaemic Index Dietsmentioning

confidence: 99%

“…Among the mechanisms that might be impairing well-managed diabetes is increased uric acid production, a product from sucrose and fructose metabolism due to the breakdown of adenine nucleotides [61]. Uric acid enters cells via specific transporters, such as URAT1, where it induces proinflammatory and prooxidative effects [62].…”

Section: Sucrose Fructose Glucose and High Glycaemic Index Dietsmentioning

confidence: 99%

Effects of the amount and type of carbohydrates used in type 2 diabetes diets in animal models: A systematic review

et al. 2020

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Type 2 diabetes mellitus (T2DM) is among the most prevalent diseases in the world, affecting over 420 million people. The disease is marked by a poor metabolic effect of insulin leading to chronic hyperglycaemia, which can result in microvascular complications. It is widely known that postprandial glycaemia is reliant on the total carbohydrate content of a meal. However, the importance of the amount and the source of these carbohydrates remains controversial due to mechanisms other than insulin secretion. Oxidative stress, inflammation, pyruvate production and the quality of the intestinal microbiota, resulting in plasma lipopolysaccharides and short-chain fatty acids production, play an important role in blood sugar control and consequently in type 2 diabetes. Thus, we systematically reviewed the preclinical evidences on the impact of the amount and type of carbohydrate found in different diets and its influence on blood glucose levels in diabetic animals. We used a comprehensive and structured search in biomedical databases Medline (PubMed), Scopus and Web of Science, recovering and analyzing 27 original studies. Results showed that sucroserich diets deteriorated diabetic condition in animal models regardless of the total dietary carbohydrate content. On the other hand, fiber, particularly resistant starch, improved blood glucose parameters through direct and indirect mechanisms, such as delayed gastric emptying and improved gut microbiota. All studies used rodents as animal models and male animals were preferred over females. Improvements in T2DM parameters in animal models were more closely related to the type of dietary carbohydrate than to its content on a diet, i. e., resistant starch seems to be the most beneficial source for maintaining normoglycemia. Results show that current literature is at high risk of bias due to neglecting experimental methods.

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“…Specifically, when compared with healthy people, patients with T2DM were found to have higher concentrations of lithocholic acid and taurocholic acid, but lower concentrations of ursodeoxycholic acid [36]. In addition, the proportion of 12αhydroxylated bile acids was found to be higher in diabetic rats and mice [37,38].…”

Section: Mechanisms Of the Effects Of Fgf19 On Glucose Metabolism Andmentioning

confidence: 99%

Serum Fibroblast Growth Factor 19 and Total Bile Acid Concentrations Are Potential Biomarkers of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus

Sun

Zhu

Zhao

et al. 2020

BioMed Research International

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Purpose. Type 2 diabetes mellitus (T2DM) carries a high risk of hepatocellular carcinoma (HCC). Both serum fibroblast growth factor 19 (FGF19) and bile acid concentrations are associated with T2DM and HCC. We aimed at evaluating the relationships between FGF19 and bile acid concentrations and HCC in patients with T2DM. Methods. Twenty-seven healthy volunteers (control group), 27 patients with T2DM (T2DM group), 16 patients with newly diagnosed HCC (HCC group), and 10 T2DM patients with newly diagnosed HCC (T2DM-HCC group) were studied at the Affiliated Hospital of Nantong University between June 2016 and June 2017. The serum concentrations of serum FGF19 and total bile acids (TBA) were measured in all the participants. Correlation analysis and multiple stepwise regression analysis of the FGF19 and TBA concentrations were performed in all the participants and in the four groups. Results. The concentrations of FGF19 were 220.5 pg/ml, 185.1 pg/ml, 115.8 pg/ml, and 70.4 pg/ml in the HCC, T2DM-HCC, control, and T2DM groups, respectively (p<0.001), and the TBA concentrations were 21.75 μmol/l, 14.25 μmol/l, 3.6 μmol/l, and 3.1 μmol/l (p<0.001). There were positive correlations between the FGF19 and TBA concentrations across all the participants (r = 0.777; p<0.001), and in the control (r = 0.400; p=0.039), T2DM (r = 0.477; p=0.012), HCC (r = 0.684; p=0.003), and T2DM-HCC (r = 0.673; p=0.033) groups. Conclusions. Simultaneous increase of serum FGF19 and TBA levels may be used as indicators of HCC screening at early stage in patients with T2DM.

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The alterations of bile acids in rats with high-fat diet/streptozotocin-induced type 2 diabetes and their negative effects on glucose metabolism

Cited by 26 publications

References 45 publications

Molecular hydrogen improves type 2 diabetes through inhibiting oxidative stress

Molecular hydrogen improves type 2 diabetes through inhibiting oxidative stress

Effects of the amount and type of carbohydrates used in type 2 diabetes diets in animal models: A systematic review

Serum Fibroblast Growth Factor 19 and Total Bile Acid Concentrations Are Potential Biomarkers of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus

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