scholarly journals Anti-Diabetic Effect of a Polysaccharide Fraction From Momordica Charantia: Modulation of Notch Signaling

Author(s):  
Soraya Sajadimajd ◽  
Bahareh Mohammadi ◽  
Gholamreza Bahrami ◽  
Seyed Hamid Madani ◽  
Razieh Hatami ◽  
...  

Abstract Given the impact of notch signaling in the modulation of metabolic diseases and normal tissue homeostasis, this study aimed to evaluate whether notch signaling has a role in anti-diabetic and islet regenerative effects of isolated polysaccharide from Memordica charantia in diabetic rats. The polysaccharide was isolated from Memordica charantia (MCP) and characterized using FTIR and LC-MS/MS. Diabetic model was established by intrapritoneal administration of STZ in male Wistar rats. The levels of Hes1, Notch 1, DLL4, Jagged1, Pdx1, CD34, CD31 and VEGF were analyzed by using immunohistochemistry and real-time PCR. Structural analyses have revealed the carbohydrate structure of fraction. Blood glucose was halted by treatment with fraction. MCP scaled up the mRNA levels of Ins1, jagged1, Pdx1 and Hes1 while scaled down the levels of Notch1, Dll4 and the ratio of Bax/Bcl2 in diabetic rats. Furthermore, the immunohistochemistry staining of hes1, cyclin d1 and VEGF proteins was increased in the pancreas of MCP-treated diabetic rats compared to the diabetic group. These findings provide insights into the anti-diabetic potential of MCP through modulation of islets regeneration and suggest that modulation of notch and angiogenesis pathways may play the pivotal role in the restoration of islets to relieve diabetes.

2015 ◽  
Vol 224 (3) ◽  
pp. 303-313 ◽  
Author(s):  
Jonathan M Mudry ◽  
Julie Massart ◽  
Ferenc L M Szekeres ◽  
Anna Krook

TWIST proteins are important for development of embryonic skeletal muscle and play a role in the metabolism of tumor and white adipose tissue. The impact of TWIST on metabolism in skeletal muscle is incompletely studied. Our aim was to assess the impact of TWIST1 and TWIST2 overexpression on glucose and lipid metabolism. In intact mouse muscle, overexpression of Twist reduced total glycogen content without altering glucose uptake. Expression of TWIST1 or TWIST2 reducedPdk4mRNA, while increasing mRNA levels ofIl6,Tnfα, andIl1β. Phosphorylation of AKT was increased and protein abundance of acetyl CoA carboxylase (ACC) was decreased in skeletal muscle overexpressing TWIST1 or TWIST2. Glycogen synthesis and fatty acid oxidation remained stable in C2C12 cells overexpressing TWIST1 or TWIST2. Finally, skeletal muscle mRNA levels remain unaltered inob/obmice, type 2 diabetic patients, or in healthy subjects before and after 3 months of exercise training. Collectively, our results indicate that TWIST1 and TWIST2 are expressed in skeletal muscle. Overexpression of these proteins impacts proteins in metabolic pathways and mRNA level of cytokines. However, skeletal muscle levels of TWIST transcripts are unaltered in metabolic diseases.


2020 ◽  
Vol 10 (6) ◽  
pp. 7011-7022 ◽  

Diabetes is a public health problem that affects life quality. Exercise training (ET) and controlled dietary habits improve metabolic diseases such as diabetes. The mechanisms by which exercise training ameliorate metabolic diseases are not fully clear. We designed the current study to evaluate the combination of ERRα suppression and ET effects on the expression of LXR-α, PDK4, and PPARα in healthy and STZ-induced diabetic rats. Fifty-six male Wistar rats were divided into 8 groups (n = 7) as follows; control, diabetic control (a single dose of 45 mg/kg of STZ), ERRα inhibition group (received 0.48 mg/kg of XCT790), endurance training, diabetic rats which received XCT790, diabetic rats which performed endurance training, rats which received XCT790 and performed endurance training, and diabetic rats which received XCT790 and also performed endurance training. Expression of the target gene and protein was carried out on the liver tissue. Our results showed that ET significantly increased PDK4, PPARα, and ERRα expression. ERRα suppression significantly increased LXR-α and PDK4 expression in healthy rats compared to the healthy control group. In the diabetic group with ERRα suppression, LXR-α expression significantly upregulated. The combination of ET and ERRα suppression did not change LXR-α expression compared to healthy and diabetic groups (CTL/ERR), but the expression of PDK4, PPARα, and ERRα was significantly upregulated.


2020 ◽  
Vol 10 (3) ◽  
pp. 71-73
Author(s):  
Ahed J Alkhatib

Introduction: Diabetes has various impacts on human body. It is thought that diabetes is predisposed by obesity. Obesity may due to several factors including genetically-environmental factors. The recent views that viruses may act as etiology for obesity. Study objectives: The main objectives of the present study were to investigate the possibility that CMV and HPV of having a role in initiating episodes of obesity and diabetes, and to test the hypothesis that co-existence of multi-viruses including corona virus may work synergistically to increase the impact of COVID-19 on diabetic patients. Methodology: In this study, a diabetic model was induced, the localization of HPV and CMV was determined using immunohistochemistry. Results: Study findings showed that both viruses HPV and CMV exist in the adipose tissue of diabetic rats. Both viruses were brown in color. Conclusions: Taken together, both CMV and HPV exist in the adipose tissue of diabetic rats, and this may explain the phenomenon of autoimmunity in diabetes from one side and from another side, we may explain the occurrence of synergistic effects of COVID-19 virus and the other viruses mentioned in this study.


Biologia ◽  
2017 ◽  
Vol 72 (8) ◽  
Author(s):  
Syed Muhammad Nurulain ◽  
Shreesh Ojha ◽  
Mohamed Shafiullah ◽  
Javed Yasin ◽  
Tayyaba Yasmin ◽  
...  

AbstractThe consequences of chronic exposure of organophosphorus compounds (OPCs) on diabetic subjects have been seldom reported. The aim of the present study was to assess the impact of non-lethal dose of terbufos sulfone (TS), an organophosphate, on the kidney of non-diabetic and streptozotocin (STZ)- induced diabetic rats. The diabetogenic effect of TS was also examined. Male Wistar rats were treated for two weeks with 130 µg/kg body weight/day of TS. This dose was 1/20 of LD


2021 ◽  
Vol 10 (3) ◽  
pp. e24-e24
Author(s):  
Shahrokh Bagheri ◽  
Mostafa Moradi Sarabi ◽  
Mohammadreza Gholami ◽  
Vahideh Assadollahi ◽  
Reza Mohammadrezaei Khorramabadi ◽  
...  

Introduction: Diabetes mellitus (DM) is a multi-factorial condition associated with oxidative stress. Limonene, as a plant-derived antioxidant, can be used for treating DM. Objectives: An investigation on antioxidant effects in diabetic rats exposed to D-limonene. Materials and Methods: Sixty male Wistar rats were categorized into six groups as follows: control (healthy rats), diabetic control (untreated diabetic rats), sham glibenclamide, diabetic glibenclamide, sham limonene, and finally diabetic limonene. Alloxan (100 mg/dL) was infused intraperitoneally to induce type 1 diabetes in rats. Rats in certain groups were given limonene (100 mg/dL) and glibenclamide (10 mg/dL) orally for 8 weeks. Subsequently, animals were killed, and their kidneys were removed. Serum levels of biochemical factors (including serum creatinine, urea, and glucose) were determined, and factors such as nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) were measured in kidney tissue homogenate. The gene expression and enzymatic activity of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in the kidney were measured by real-time polymerase chain reaction (real-time PCR) and spectrophotometry, respectively. Results: Limonene treatment significantly decreased serum glucose, creatinine, and urea. Additionally, MDA, MPO, and NO significantly decreased while GSH increased after treatment with limonene. Real-time RT-PCR showed significant elevation (P<0.05) in mRNA levels of GPx, CAT, and SOD in the limonene-treated compared with the diabetic control group. Conclusion: Our results demonstrated that limonene as an herbal antioxidant had better effects on antioxidant markers compared to glibenclamide in rat models of diabetes.


2005 ◽  
Vol 185 (3) ◽  
pp. 457-465 ◽  
Author(s):  
Patrice D Cani ◽  
Catherine A Daubioul ◽  
Brigitte Reusens ◽  
Claude Remacle ◽  
Grégory Catillon ◽  
...  

We have evaluated the influence of oligofructose (OFS), a fermentable dietary fibre, on glucose homeostasis, insulin production and intestinal glucagon-like peptide-1 (GLP-1) in streptozotocin-treated diabetic rats. Male Wistar rats received either i.v. streptozotocin (STZ; 40 mg/kg) or vehicle (CT); one week later, they were fed for 6 weeks with either the standard diet (STZ-CT), or with a diet containing 10% oligofructose (STZ-OFS); both diets were available ad libitum. In a second set of experiments (duration 4 weeks), a supplemental group of food-restricted rats (STZ-Res) receiving a similar intake as CT rats, was added. OFS improved glucose tolerance and reduced food intake as compared with STZ-CT rats in both the post-prandial state and after an oral glucose tolerance test. After 6 weeks, portal and pancreatic insulin concentrations were doubled in STZ-OFS rats. Food restriction improved these parameters when compared with STZ-CT rats, but to a lesser extent than in the STZ-OFS group. We have shown that OFS treatment increased portal and colonic GLP-1(7–36) amide levels and doubled colonic proglucagon and prohormone convertase 1 mRNA levels; both OFS and food restriction lowered ileal GLP-1(7–36) amide levels as compared with levels in STZ-CT rats. We propose that OFS, through its fermentation in the colon, promotes the expression and secretion of colonic peptides, namely GLP-1(7–36) amide, with beneficial consequences on glycaemia, insulin secretion and hyperphagia in diabetic rats.


Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2582
Author(s):  
Paula K. N. Alves ◽  
André Cruz ◽  
William J. Silva ◽  
Siegfried Labeit ◽  
Anselmo S. Moriscot

In this study we surveyed a rat skeletal muscle RNA-Seq for genes that are induced by hindlimb immobilization and, in turn, become attenuated by leucine supplementation. This approach, in search of leucine-atrophy protection mediating genes, identified histone deacetylase 4 (HDAC4) as highly responsive to both hindlimb immobilization and leucine supplementation. We then examined the impact of leucine on HDAC4 expression, tissue localization, and target genes. A total of 76 male Wistar rats (~280 g) were submitted to hindlimb immobilization and/or leucine supplementation for 3, 7 and 12 days. These animals were euthanized, and soleus muscle was removed for further analysis. RNA-Seq analysis of hindlimb immobilized rats indicated a sharp induction (log2 = 3.4) of HDAC4 expression which was attenuated by leucine supplementation (~50%). Real-time PCR and protein expression analysis by Western blot confirmed increased HDAC4 mRNA after 7 days of hindlimb immobilization and mitigation of induction by leucine supplementation. Regarding the HDAC4 localization, the proportion of positive nuclei was higher in the immobilized group and decreased after leucine supplementation. Also, we found a marked decrease of myogenin and MAFbx-atrogin-1 mRNA levels upon leucine supplementation, while CAMKII and DACH2 mRNA levels were increased by leucine supplementation. Our data suggest that HDAC4 inhibition might be involved in the anti-atrophic effects of leucine.


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Lulu Wang ◽  
Guanglan Duan ◽  
Yong Lu ◽  
Shuguang Pang ◽  
Xianping Huang ◽  
...  

Objective. To investigate the effect of simvastatin on glucose homeostasis in streptozotocin induced type 2 diabetic rats.Methods. Forty male Wistar rats were randomly divided into four groups. Normal control rats were fed with standard diet, others were fed with high-fat diet. Diabetic rats were induced by a single intraperitoneal injection of STZ. The simvastatin intervention rats were fed with simvastatin during the experiment process, and the simvastatin treatment rats were fed with simvastatin after diabetes rats were induced. We measured body weight, fasting plasma glucose, cholesterol, high-density lipoprotein cholesterol, and triglyceride after an overnight fast.Results. The FPG was higher in diabetic rats when compared to normal control ones; the simvastatin intervention rats had a higher FPG compared to the diabetic rats and were more easily be induced to diabetes at the end of 4 weeks, FPG level of simvastatin treatment rats was increased compared with diabetic model rats after 12 weeks.Conclusion. These data indicate that simvastatin intervention rats may cause hyperglycemia by impairing the function of isletβcells and have an adverse effect on glucose homeostasis, especially on FPG level.


2019 ◽  
Vol 16 (1) ◽  
pp. 14
Author(s):  
Azka Darajat ◽  
Elly Nurus Sakinah ◽  
Hairrudin Hairrudin

Effect of analog rice’s fiber on skeletal muscles GLUT4 expression in diabetic rats Background: Disruption of glucose transportation in skeletal muscle through GLUT4 becomes a problem in diabetes. Analog rice that had been modified by adding dietary fiber could improve the expression of GLUT4.Objective: This study aims to know the effect of dietary fiber toward GLUT4 expression and to know the dietary fiber percentage in analog rice.Method: The research type is true experimental with post-test only group design. The samples consist of 24 male Wistar rats that are group into 4 groups (n=6 each group). Three groups were induced by giving a high-fat diet for 40 days and streptozotocin (STZ) 35 mg/kg BW was given at 33th day and one group was not induced. After the blood glucose level exceeded 135 mg/dl, the treatment was given. After 3 weeks, the rats were terminated and quadriceps femoris muscle tissue was taken for immunohistochemistry examination using rat GLUT4 polyclonal antibody. GLUT4 expression was quantified using an immunoreactive score (IRS-GLUT4). The data were analyzed using the Kruskal-Wallis test and Spearman test.Results: Statistical analyses showed that there were significant differences between groups with a moderate positive correlation (correlation coefficient=0,651; p=0,003).Conclusion: Dietary fiber in analog rice could improve skeletal muscle GLUT4 expression in Wistar rat diabetic model.


2015 ◽  
Vol 2015 ◽  
pp. 1-11
Author(s):  
Aleksandra Wyczalkowska-Tomasik ◽  
Irena Bartlomiejczyk ◽  
Agnieszka Wirkowska ◽  
Lukasz Koperski ◽  
Barbara Gornicka ◽  
...  

Hyperglycemia results in the activation of tissue angiotensin II. Angiotensin II stimulates the synthesis of ECM proteins and causes a decrease activity of proteolytic enzymes. The aim of this study was to assess the impact of multilevel blocking of the RAAS, cathepsin B activity, and fibronectin accumulation in the glomerular in the rats diabetes model. Sixty male Wistar rats were initially included. Diabetes was induced by intravenous administration of streptozotocin. The animals were randomized to six groups of ten rats in group. Rats in the four groups were treated with inhibitors of the RAAS: enalapril (EN), losartan (LOS), enalapril plus losartan (EN+LOS), and spironolactone (SPIR); another group received dihydralazine (DIH) and the diabetic rats (DM) did not receive any drug. After six weeks, we evaluated blood pressure, 24 h urine collection, and blood for biochemical parameters and kidneys. In this study, fluorometric, ELISA, and immunohistochemical methods were used. Administration of EN+LOS increased activity of cathepsin B in homogenates of glomeruli compared to DM. Losartan treatment resulted in reduction of the ratio kidney weight/body weight compared to untreated diabetic rats. SPIR resulted in the increase activity of cathepsin B in the homogenate of glomeruli. The values of cathepsin B in the plasma of rats in all studied groups were similar and showed no tendency.


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