Glutathione Deficiency Induces Epigenetic Alterations of Vitamin D Metabolism Genes in the Liver of High-Fat Diet–Induced Type 2 Diabetic Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1878-P ◽  
Author(s):  
RAJESH PARSANATHAN ◽  
SUSHIL K. JAIN
Keyword(s):  
Vitamin D ◽  
High Fat Diet ◽  
Epigenetic Alterations ◽  
Diabetic Mice ◽  
High Fat ◽  
Vitamin D Metabolism ◽  
Glutathione Deficiency ◽  
Type 2 Diabetic

scholarly journals Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rajesh Parsanathan ◽  
Sushil K. Jain
Keyword(s):  
Vitamin D ◽  
High Fat Diet ◽  
Control Diet ◽  
Epigenetic Alterations ◽  
Obese Mice ◽  
High Fat ◽  
Vitamin D Metabolism ◽  
Potential Benefits ◽  
Low Levels ◽  
Glutathione Deficiency

Abstract Obesity has been correlating with low levels of glutathione (GSH) and 25-hydroxyvitamin D3 (25(OH)VD3). The liver is the principal site for the 25(OH)VD3 biosynthesis. This study investigated whether GSH deficiency induces epigenetic alterations that impair Vitamin D (VD) metabolism genes in the livers of HFD-fed mice. The expression of the VD metabolism genes CYP2R1 and CYP27A1 (25-hydroxylase), CYP27B1 (1-α-hydroxylase), and vitamin D receptor (VDR) were downregulated in the livers of mice fed an HFD (GSH- deficient) compared with control diet-fed group. The expression of CYP24A1 (24-hydroxylase) was significantly increased, which catabolizes both 25(OH)VD3 and 1α,25-hydroxyvitaminD3. Gene-specific hypermethylation of 25-hydroxylase, 1-α-hydroxylase, and VDR, and hypomethylation of CYP24A1 was observed in HFD-fed mice. GSH deficiency induced in cultured hepatocytes caused an increase in oxidative stress and alterations in VD regulatory genes. Similarly, elevated global DNA methylation, Dnmt activity, and 5-methylcytosine but decreased Tet activity and 5-hydroxymethylcytosine were observed in the GSH-deficient hepatocytes and the liver of HFD-fed mice. Replenishment of GSH by its prodrugs treatment beneficially altered epigenetic enzymes, and VD-metabolism genes in hepatocytes. HFD-induces GSH deficiency and epigenetically alters VD-biosynthesis pathway genes. This provides a biochemical mechanism for the VD-deficiency and potential benefits of GSH treatment in reducing 25(OH)VD3-deficiency.

scholarly journals Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 159 ◽  
Author(s):  
Kyung-Ah Park ◽  
Zhen Jin ◽  
Jong Youl Lee ◽  
Hyeong Seok An ◽  
Eun Bee Choi ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Fusion Protein ◽  
High Fat Diet ◽  
Memory Deficits ◽  
Receptor Expression ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
High Fat ◽  
Type 2 Diabetic

Glucagon-like peptide 1 (GLP-1) mimetics have been approved as an adjunct therapy for glycemic control in type 2 diabetic patients for the increased insulin secretion under hyperglycemic conditions. Recently, it is reported that such agents elicit neuroprotective effects against diabetes-associated cognitive decline. However, there is an issue of poor compliance by multiple daily subcutaneous injections for sufficient glycemic control due to their short duration, and neuroprotective actions were not fully studied, yet. In this study, using the prepared exendin-4 fusion protein agent, we investigated the pharmacokinetic profile and the role of this GLP-1 mimetics on memory deficits in a high-fat diet (HFD)/streptozotocin (STZ) mouse model of type 2 diabetic mellitus. After induction of diabetes, mice were administered weekly by intraperitoneal injection of GLP-1 mimetics for 6 weeks. This treatment reversed HFD/STZ-induced metabolic symptoms of increased body weight, hyperglycemia, and hepatic steatosis. Furthermore, the impaired cognitive performance of diabetic mice was significantly reversed by GLP-1 mimetics. GLP-1 mimetic treatment also reversed decreases in GLP-1/GLP-1 receptor expression levels in both the pancreas and hippocampus of diabetic mice; increases in hippocampal inflammation, mitochondrial fission, and calcium-binding protein levels were also reversed. These findings suggest that GLP-1 mimetics are promising agents for both diabetes and neurodegenerative diseases that are associated with increased GLP-1 expression in the brain.

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.

Antidiabetic Effect of Sargassum wightii and Ulva fasciata in High Fat Diet and Multi Low Dose Streptozotocin Induced Type 2 Diabetic Mice

2016 ◽  
Vol 4 (2) ◽  
pp. 13 ◽  
Author(s):  
Lucy Mohapatra ◽  
Subrat Kumar Bhattamishra ◽  
Ramachandra Panigrahy ◽  
Sambit Parida ◽  
Premalata Pati
Keyword(s):  
High Fat Diet ◽  
Low Dose ◽  
Diabetic Mice ◽  
High Fat ◽  
Antidiabetic Effect ◽  
Ulva Fasciata ◽  
Sargassum Wightii ◽  
Type 2 Diabetic

Protective role of adiponectin against testicular impairment in high-fat diet/streptozotocin-induced type 2 diabetic mice

Biochimie ◽  
2020 ◽  
Vol 168 ◽  
pp. 41-52 ◽  
Author(s):  
Mayank Choubey ◽  
Ashutosh Ranjan ◽  
Puran S. Bora ◽  
Amitabh Krishna
Keyword(s):  
High Fat Diet ◽  
Protective Role ◽  
Diabetic Mice ◽  
High Fat ◽  
Testicular Impairment ◽  
Type 2 Diabetic

Isoflurane aggravates peripheral and central insulin resistance in high-fat diet/streptozocin-induced type 2 diabetic mice

2020 ◽  
Vol 1727 ◽  
pp. 146511 ◽  
Author(s):  
Xin Fang ◽  
Tianjiao Xia ◽  
Fangxia Xu ◽  
Hao Wu ◽  
Zhengliang Ma ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Diabetic Mice ◽  
High Fat ◽  
Type 2 Diabetic

scholarly journals Effect of endurance exercise on oxidative stress marker malondialdehyde in type 2 diabetic mice.

2020 ◽  
Vol 27 (07) ◽  
pp. 1493-1498
Author(s):  
Sana Akram ◽  
Maimona Tabssum ◽  
Maryam Rao ◽  
Hamid Javaid Qureshi
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Endurance Exercise ◽  
High Fat Diet ◽  
Exercise Program ◽  
Oxidative Stress Marker ◽  
Diabetic Mice ◽  
High Fat ◽  
Type 2 Diabetic

Diabetes is associated with oxidative stress and has a significant role in the pathophysiology of the disease and its complications. Exercise training is a powerful therapeutic approach in diabetes and has protective effects against the progress of its complications. Objectives: The aim of this study was to investigate the effect of an endurance exercise program on the oxidative stress marker malondialdehyde (MDA) in high fat diet-low dose streptozotocin induced type 2 diabetic mouse model. Study Design: Randomized Control trial. Setting: Department of Physiology, Akhtar Saeed Medical and Dental College, Lahore. Period: August 2017 to August 2018. Material & Methods: 60 male albino mice were fed a high fat diet containing 60% kCal as fat for 4 weeks. This was followed by intra peritoneal injection of 40mg/kg body weight streptozotocin, given on three consecutive days. Mice with fasting blood glucose more than 250mg/dl after a week were considered diabetic. Half the mice underwent an exercise program which comprised of a 20 minute swimming session per day, with a 6% body weight load attached to the tail of mice, 3 days a week, for 4 weeks. The level of MDA was estimated in both groups using TBARs method. Results: Mean malondialdehyde level was significantly (p˂0.05) reduced in diabetic mice that underwent endurance exercise training. Conclusion: This study highlights the important role of endurance exercise in reducing oxidative stress in diabetes.

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