Effect of thymoquinone on high fat diet and STZ‐induced experimental type 2 diabetes: A mechanistic insight by in vivo and in silico studies

2021 ◽  
Author(s):  
Saeed Alshahrani ◽  
Tarique Anwer ◽  
Mohammad Firoz Alam ◽  
Rayan A. Ahmed ◽  
Gyas Khan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
In Silico ◽  
High Fat Diet ◽  
High Fat ◽  
Mechanistic Insight ◽  
In Silico Studies ◽  
Experimental Type

scholarly journals TRAIL reduces impaired glucose tolerance and NAFLD in the high-fat diet fed mouse

2018 ◽  
Vol 132 (1) ◽  
pp. 69-83 ◽  
Author(s):  
Stella Bernardi ◽  
Barbara Toffoli ◽  
Veronica Tisato ◽  
Fleur Bossi ◽  
Stefania Biffi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
High Fat Diet ◽  
Disease Onset ◽  
High Fat ◽  
Primary Hepatocytes

Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis inducing ligand) may have an important role in the treatment of type 2 diabetes. It has been shown that TRAIL deficiency worsens diabetes and that TRAIL delivery, when it is given before disease onset, slows down its development. The present study aimed at evaluating whether TRAIL had the potential not only to prevent, but also to treat type 2 diabetes. Thirty male C57BL/6J mice were randomized to a standard or a high-fat diet (HFD). After 4 weeks of HFD, mice were further randomized to receive either placebo or TRAIL, which was delivered weekly for 8 weeks. Body weight, food intake, fasting glucose, and insulin were measured at baseline and every 4 weeks. Tolerance tests were performed before drug randomization and at the end of the study. Tissues were collected for further analyses. Parallel in vitro studies were conducted on HepG2 cells and mouse primary hepatocytes. TRAIL significantly reduced body weight, adipocyte hypertrophy, free fatty acid levels, and inflammation. Moreover, it significantly improved impaired glucose tolerance, and ameliorated non-alcoholic fatty liver disease (NAFLD). TRAIL treatment reduced liver fat content by 47% in vivo as well as by 45% in HepG2 cells and by 39% in primary hepatocytes. This was associated with a significant increase in liver peroxisome proliferator-activated receptor (PPAR) γ (PPARγ) co-activator-1 α (PGC-1α) expression both in vivo and in vitro, pointing to a direct protective effect of TRAIL on the liver. The present study confirms the ability of TRAIL to significantly attenuate diet-induced metabolic abnormalities, and it shows for the first time that TRAIL is effective also when administered after disease onset. In addition, our data shed light on TRAIL therapeutic potential not only against impaired glucose tolerance, but also against NAFLD.

scholarly journals The Antiinflammatory Cytokine Interleukin-1 Receptor Antagonist Protects from High-Fat Diet-Induced Hyperglycemia

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2208-2218 ◽  
Author(s):  
Nadine S. Sauter ◽  
Fabienne T. Schulthess ◽  
Ryan Galasso ◽  
Lawrence W. Castellani ◽  
Kathrin Maedler
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Receptor Antagonist ◽  
High Fat Diet ◽  
Cell Function ◽  
Interleukin 1 ◽  
High Fat ◽  
Β Cell

Subclinical inflammation is a recently discovered phenomenon in type 2 diabetes. Elevated cytokines impair β-cell function and survival. A recent clinical trial shows that blocking IL-1β signaling by IL-1 receptor antagonist (IL-1Ra) improves β-cell secretory function in patients with type 2 diabetes. In the present study, we provide further mechanisms of the protective role of IL-1Ra on the β-cell. IL-1Ra prevented diabetes in vivo in C57BL/6J mice fed a high-fat/high-sucrose diet (HFD) for 12 wk; it improved glucose tolerance and insulin secretion. High-fat diet treatment increased serum levels of free fatty acids and of the adipokines resistin and leptin, which were reduced by IL-1Ra treatment. In addition, IL-1Ra counteracted adiponectin levels, which were decreased by high-fat feeding. Studies on isolated islets revealed that IL-1Ra specifically acted on the β-cell. IL-1Ra protected islets from HFD treated animals from β-cell apoptosis, induced β-cell proliferation, and improved glucose-stimulated insulin secretion. Insulin mRNA was reduced in islets from mice fed a HFD but normalized in the IL-1Ra group. Our results show that IL-1Ra improves β-cell survival and function, and support the potential role for IL-1Ra in the treatment of diabetes.

scholarly journals Synthesis, Spectral Characterization, and Biochemical Evaluation of Antidiabetic Properties of a New Zinc-Diosmin Complex Studied in High Fat Diet Fed-Low Dose Streptozotocin Induced Experimental Type 2 Diabetes in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Veerasamy Gopalakrishnan ◽  
Subramanian Iyyam Pillai ◽  
Sorimuthu Pillai Subramanian
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Low Dose ◽  
Diabetic Rats ◽  
Spectral Studies ◽  
Oral Glucose ◽  
High Fat ◽  
Experimental Type

In view of the established antidiabetic properties of zinc, the present study was aimed at evaluating the hypoglycemic properties of a new zinc-diosmin complex in high fat diet fed-low dose streptozotocin induced experimental type 2 diabetes in rats. Zinc-diosmin complex was synthesized and characterized by various spectral studies. The complexation between zinc ions and diosmin was further evidenced by pH-potentiometric titrations and Job’s plot. Diabetic rats were orally treated with zinc-diosmin complex at a concentration of 20 mg/kg b.w./rat/day for 30 days. At the end of the experimental period, the rats were subjected to oral glucose tolerance test. In addition, HOMA-IR and various biochemical parameters related to glucose homeostasis were analyzed. Treatment with zinc-diosmin complex significantly improved the glucose homeostasis in diabetic rats. Treatment with zinc-diosmin complex significantly improved insulin sensitivity, at least in part, through enhancing protein metabolism and alteration in the levels of muscle and liver glycogen. The assay of clinical marker enzymes revealed the nontoxic nature of the complex. Determination of renal tissue markers such as blood urea and serum creatinine indicates the renoprotective nature of the complex. These findings suggest that zinc-diosmin complex is nontoxic and has complimentary potential to develop as an antihyperglycemic agent for the treatment of diabetes mellitus.

scholarly journals ALOE-EMODIN GLYCOSIDES AMELIORATE GLUCOSE UTILIZATION VIA INSULIN DOWNSTREAM REGULATORS: AN IN VIVO INVESTIGATION

2016 ◽  
pp. 191 ◽  
Author(s):  
Singaravelu Anand ◽  
Saravanababu C ◽  
Lakshmi Bs ◽  
Muthusamy Vs
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Receptor ◽  
Carbohydrate Metabolism ◽  
High Fat Diet ◽  
Low Dose ◽  
Diabetic Rats ◽  
High Fat ◽  
Aloe Emodin

<p>ABSTRACT<br />Objective: Aloe-emodin glycosides (AEG) isolated from Cassia fistula stimulates glucose transport and glycogen storage through a phosphatidylinositol<br />3 kinase (PI3K)-dependent mechanism in L6 myotubes and inhibits adipocytes differentiation in 3T3L1 adipocytes was previously reported. This<br />study intended to investigate the insulin mimetic effect of AEG by in vivo method.<br />Methods: Male Wistar albino rats were randomly allocated into two groups and fed for a period of 3-week. The high-fat diet group animals were<br />injected with a low dose (35 mg/kg) of streptozotocin to induce Type-2 diabetes. The diabetic rats were then treated with low dose: 10 mg/kg and<br />high dose: 30 mg/kg for a period of 21-day. A dose-dependent decrease in fasting blood glucose, cholesterol, and triglycerides levels on treatment<br />with AEG. The carbohydrate metabolism in diabetic rats appeared to improve due to regulation in hepatic enzymes such as hexokinase, glucose-6phosphatase,<br />and fructose<br />1,6-bisphosphatase with a concomitant increase<br />in glycogen<br />content.<br />Results: AEG decreased lipid peroxidation and improved the antioxidant (enzymatic and nonenzymatic) levels in the liver of diabetic rats. Treatment<br />with AEG (30 mg/kg) augmented the phosphorylation of insulin downstream regulators such as insulin receptor beta, insulin receptor substrate 1,<br />PI3K, glucose transporter 4, glycogen synthase kinase 3 beta, and peroxisome proliferator activator receptor gamma in the skeletal muscle tissue of<br />the Type-2 diabetic rats compared to vehicle-treated diabetic rats.<br />Conclusion: The present results suggested that AEG could serve as an interesting candidate in the drug development for the management of diabetes.<br />Keywords: Aloe-emodin glycoside, Type-2 diabetes, High-fat diet/streptozotocin, Carbohydrate Metabolism, Glycogen, Antioxidant enzyme.</p>

Induction and rescue of skeletal fragility in a high-fat diet mouse model of type 2 diabetes: An in vivo and in vitro approach

Bone ◽  
2021 ◽  
pp. 116302
Author(s):  
Joan E. LLabre ◽  
Grażyna E. Sroga ◽  
Matthew J.L. Tice ◽  
Deepak Vashishth
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
High Fat Diet ◽  
High Fat ◽  
Skeletal Fragility
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