scholarly journals Uninephrectomized High-Fat-Fed Nicotinamide-Streptozotocin-Induced Diabetic Rats: A Model for the Investigation of Diabetic Nephropathy in Type 2 Diabetes

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Valentina K. Bayrasheva ◽  
Alina Yu. Babenko ◽  
Vladimir A. Dobronravov ◽  
Yuri V. Dmitriev ◽  
Svetlana G. Chefu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Rat Model ◽  
Diabetic Rats ◽  
Metabolic Parameters ◽  
Tubular Injury ◽  
High Fat ◽  
Alimentary Obesity ◽  
Normal Chow ◽  
Male Wistar Rats

Type 2 diabetes (DM2) could be reproduced in rats with alimentary obesity by using low doses of streptozotocin (LD-STZ) as well as STZ in high doses with preliminary nicotinamide (NA) administration. However, STZ could induce tubulotoxicity.Aim. To develop rat model of DN in NA-STZ-induced DM2 and compare it with LD-STZ-model in order to choose the most relevant approach for reproducing renal glomerular and tubular morphofunctional diabetic changes. Starting at 3 weeks after uninephrectomy, adult male Wistar rats were fed five-week high-fat diet and then received intraperitoneally either LD-STZ (40 mg/kg) or NA (230 mg/kg) followed by STZ (65 mg/kg). Control uninephrectomized vehicle-injected rats received normal chow. At weeks 10, 20, and 30 (the end of the study), metabolic parameters, creatinine clearance, albuminuria, and urinary tubular injury markers (NGAL, KIM-1) were evaluated as well as renal ultrastructural and light microscopic changes at weeks 20 and 30. NA-STZ-group showed higher reproducibility and stability of metabolic parameters. By week 10, in NA-STZ-group NGAL level was significantly lower compared to LD-STZ-group. By week 30, diabetic groups showed early features of DN. However, morphofunctional changes in NA-STZ-group appeared to be more pronounced than those in STZ-group despite lower levels of KIM-1 and NGAL. We proposed a new rat model of DM2 with DN characterized by stable metabolic disorders, typical renal lesions, and lower levels of tubular injury markers as compared to LD-STZ-induced diabetes.

scholarly journals Role of TLR4/MyD88/NF-κB signaling in heart and liver-related complications in a rat model of type 2 diabetes mellitus

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199759
Author(s):  
Jiajia Tian ◽  
Yanyan Zhao ◽  
Lingling Wang ◽  
Lin Li
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Rat Model ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Primary Response ◽  
Monocyte Chemoattractant Protein 1

Aims To analyze expression of members of the Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB signaling pathway in the heart and liver in a rat model of type 2 diabetes mellitus (T2DM). Our overall goal was to understand the underlying pathophysiological mechanisms. Methods We measured fasting blood glucose (FBG) and insulin (FINS) in a rat model of T2DM. Expression of members of the TLR4/MyD88/NF-κB signaling pathway as well as downstream cytokines was investigated. Levels of mRNA and protein were assessed using quantitative real-time polymerase chain reaction and western blotting, respectively. Protein content of tissue homogenates was assessed using enzyme-linked immunosorbent assays. Results Diabetic rats had lower body weights, higher FBG, higher FINS, and higher intraperitoneal glucose tolerance than normal rats. In addition, biochemical indicators related to heart and liver function were elevated in diabetic rats compared with normal rats. TLR4 and MyD88 were involved in the occurrence of T2DM as well as T2DM-related heart and liver complications. TLR4 caused T2DM-related heart and liver complications through activation of NF-κB. Conclusions TLR4/MyD88/NF-κB signaling induces production of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, leading to the heart- and liver-related complications of T2DM.

scholarly journals The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Kira V. Derkach ◽  
Vera M. Bondareva ◽  
Oxana V. Chistyakova ◽  
Lev M. Berstein ◽  
Alexander O. Shpakov
Keyword(s):  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Low Dose ◽  
Diabetic Rats ◽  
Brain Serotonin ◽  
Serotonin Level ◽  
High Fat ◽  
Brain Serotonin Level ◽  
The Brain

In the last years the treatment of type 2 diabetes mellitus (DM2) was carried out using regulators of the brain signaling systems. In DM2 the level of the brain serotonin is reduced. So far, the effect of the increase of the brain serotonin level on DM2-induced metabolic and hormonal abnormalities has been studied scarcely. The present work was undertaken with the aim of filling this gap. DM2 was induced in male rats by 150-day high-fat diet and the treatment with low dose of streptozotocin (25 mg/kg) on the 70th day of experiment. From the 90th day, diabetic rats received for two months intranasal serotonin (IS) at a daily dose of 20 μg/rat. The IS treatment of diabetic rats decreased the body weight, and improved glucose tolerance, insulin-induced glucose utilization, and lipid metabolism. Besides, it restored hormonal regulation of adenylyl cyclase (AC) activity in the hypothalamus and normalized AC stimulation byβ-adrenergic agonists in the myocardium. In nondiabetic rats the same treatment induced metabolic and hormonal alterations, some of which were similar to those in DM2 but expressed to a lesser extent. In conclusion, the elevation of the brain serotonin level may be regarded as an effective approach to treat DM2 and its complications.

scholarly journals Cardiac metabolism in a new rat model of type 2 diabetes using high-fat diet with low dose streptozotocin

2013 ◽  
Vol 12 (1) ◽  
pp. 136 ◽  
Author(s):  
Latt S Mansor ◽  
Eileen R Gonzalez ◽  
Mark A Cole ◽  
Damian J Tyler ◽  
Jessica H Beeson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Rat Model ◽  
High Fat Diet ◽  
Low Dose ◽  
Cardiac Metabolism ◽  
High Fat

scholarly journals Experimental Type 2 Diabetes Induces Enzymatic Changes in Isolated Rat Enterocytes

2003 ◽  
Vol 4 (2) ◽  
pp. 119-123 ◽  
Author(s):  
Isabel M. Martínez ◽  
Inmaculada Morales ◽  
Guadalupe García-Pino ◽  
José E. Campillo ◽  
María A. Tormo
Keyword(s):  
Type 2 Diabetes ◽  
Small Intestine ◽  
Glucose Absorption ◽  
Diabetic Rats ◽  
Male Wistar Rats ◽  
Experimental Type ◽  
Enzymatic Changes ◽  
Rat Enterocytes ◽  
Intestinal Disaccharidases

Diabetes in humans and in experimental animals produces changes in the function and structure of the small intestine. The authors determined the activity of intestinal disaccharidases (maltase and sucrase) and of 6-phosphofructo-1-kinase (PFK-1) in enterocytes isolated from the small intestine of male Wistar rats (2.5 to 3 months old) with experimental nonobese type 2 diabetes, induced by streptozotocin (STZ) injection on the day of birth (n0-STZ) or on the 5th day of life (n5-STZ), with different degrees of hyperglycemia and insulinemia (n0-STZ and n5-STZ models). The glycemia (mmol/L) of the diabetic rats (n0-STZ: 8.77 ± 0.47; n5-STZ: 20.83 ± 0.63) was higher (P< .01) than that of the nondiabetic (ND) rats (5.99 ± 0.63); on the contrary, the insulinemia (ng/mL) was significantly lower in both n0-STZ (1.74 ± 0.53;P< .05) and n5-STZ (1.12 ± 0.44;P< .01) diabetic rats than in normal rats (3.77 ± 0.22). The sucrase and maltase activities (U/g protein) in diabetic rats (n0-STZ: 89 ± 9 and 266 ± 12; n5-STZ: 142 ± 23 and 451 ± 57) were significantly higher than those in the ND group (66 ± 5 and 228 ± 22). The PFK-1 activities (mU/mg protein) in the diabetic models (n0-STZ: 14.89 ± 1.51; n5-STZ: 13.35 ± 3.12) were significantly lower (P< .05) than in ND rats (20.54 ± 2.83). The data demonstrated enzymatic alterations in enterocytes isolated fromthe small intestine of n0-STZ rats that are greater (P< .05) than in the more hyperglycemic and hypoinsulinemic n5-STZ animals. The results also show that nonobese type 2–like diabetes in the rat produces modifications that favor an increase in glucose absorption rates.

Lactobacillus rhamnosus NCDC17 ameliorates type-2 diabetes by improving gut function, oxidative stress and inflammation in high-fat-diet fed and streptozotocintreated rats

2017 ◽  
Vol 8 (2) ◽  
pp. 243-255 ◽  
Author(s):  
S. Singh ◽  
R.K. Sharma ◽  
S. Malhotra ◽  
R. Pothuraju ◽  
U.K. Shandilya
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Lactobacillus Rhamnosus ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Lipoprotein Cholesterol ◽  
High Fat ◽  
Epididymal Fat

Restoration of dysbiosed gut microbiota through probiotic may have profound effect on type 2 diabetes. In the present study, rats were fed high fat diet (HFD) for 3 weeks and injected with low dose streptozotocin to induce type 2 diabetes. Diabetic rats were then fed Lactobacillus rhamnosus NCDC 17 and L. rhamnosus GG with HFD for six weeks. L. rhamnosus NCDC 17 improved oral glucose tolerance test, biochemical parameters (fasting blood glucose, plasma insulin, glycosylated haemoglobin, free fatty acids, triglycerides, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol), oxidative stress (thiobarbituric acid reactive substance and activities of catalase, superoxide dismutase and glutathione peroxidase in blood and liver), bifidobacteria and lactobacilli in cecum, expression of glucagon like peptide-1 producing genes in cecum, and adiponection in epididymal fat, while decreased propionate proportions (%) in caecum, and expression of tumour necrosis factor-α and interlukin-6 in epididymal fat of diabetic rats as compared to diabetes control group. These findings offered a base for the use of L. rhamnosus NCDC 17 for the improvement and early treatment of type 2 diabetes.

scholarly journals Protective effect of crocin and voluntary exercise against oxidative stress in the heart of high-fat diet-induced type 2 diabetic rats

2016 ◽  
Vol 103 (4) ◽  
pp. 459-468 ◽  
Author(s):  
V Ghorbanzadeh ◽  
M Mohammadi ◽  
G Mohaddes ◽  
H Dariushnejad ◽  
L Chodari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Critical Role ◽  
Diabetic Rats ◽  
Voluntary Exercise ◽  
High Fat ◽  
The Impact ◽  
Type 2 Diabetic

Background Oxidative stress plays a critical role in the pathogenesis and progression of type 2 diabetes and diabetic-associated cardiovascular complications. This study investigated the impact of crocin combined with voluntary exercise on heart oxidative stress indicator in high-fat diet-induced type 2 diabetic rats. Materials and methods Rats were divided into four groups: diabetes, diabetic-crocin, diabetic-voluntary exercise, diabetic-crocin-voluntary exercise. Type 2 diabetes was induced by high-fat diet (4 weeks) and injection of streptozotocin (intraperitoneally, 35 mg/kg). Animals received crocin orally (50 mg/kg); voluntary exercise was performed alone or combined with crocin treatment for 8 weeks. Finally, malondialdehyde (MDA), activity of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured spectrophotometrically. Results Treatment of diabetic rats with crocin and exercise significantly decreased the levels of MDA (p < 0.001) and increased the activity of SOD, GPx, and CAT compared with the untreated diabetic group. In addition, combination of exercise and crocin amplified their effect on antioxidant levels in the heart tissue of type 2 diabetic rats. Conclusion We suggest that a combination of crocin with voluntary exercise treatment may cause more beneficial effects in antioxidant defense system of heart tissues than the use of crocin or voluntary exercise alone.

Comparison of mandibular trabecular structures between normal and diabetic rats: evaluation of spontaneous type 2 diabetes in a rat model

2011 ◽  
Vol 27 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Kazuo Onoyama ◽  
Ryota Kawamata ◽  
Yusuke Kozai ◽  
Takashi Sakurai ◽  
Isamu Kashima
Keyword(s):  
Type 2 Diabetes ◽  
Rat Model ◽  
Diabetic Rats

scholarly journals EFFECT OF SILYMARIN ON INTESTINAL ALKALINE PHOSPHATASE LEVEL IN A RAT MODEL OF TYPE 2 DIABETES MELLITUS: STREPTOZOTOCIN AND HIGH-FAT DIET TREATED WISTAR RATS

2018 ◽  
Vol 11 (11) ◽  
pp. 304
Author(s):  
Lalitha V ◽  
Sivakumar T
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Alkaline Phosphatase ◽  
Lipid Profile ◽  
High Fat Diet ◽  
Wistar Rats ◽  
Diabetic Rats ◽  
High Fat ◽  
Intestinal Alkaline Phosphatase

Objective: This research elucidated the role of silymarin on intestinal alkaline phosphatase (IAP) level in type 2 diabetic rats.Methods: The type 2 diabetes mellitus was induced by a high-fat diet (HFD - 58% calories fat) for 2 weeks, and rats were intraperitoneally injected with streptozotocin (STZ) 35 mg/kg. Wistar rats were divided into four groups. Group I served as a non-diabetic (normal), Group II served as diabetic, Group III diabetic animals treated glibenclamide 600 μg/kg for 14 days, and Group IV diabetic animal treated with glibenclamide and silymarin 50 mg/kg/twice/d for 14 days. At the end of the study, blood glucose, lipid profile, and IAP level were measured.Results: A significant decrease in IAP, elevated levels of blood glucose, and lipid profile was seen in diabetic rats when compared with normal. The silymarin treatment showed a significant increase in IAP level, a significant reduction in glucose and lipid profile than diabetic rats.Conclusion: The present study concludes that silymarin treatment enhances the IAP levels which protect against hyperglycemia, hyperlipidemia, and vascular complications in diabetic rats.

scholarly journals Gymnemic acid, a potent antidiabetic agent protects skeletal muscle from hyperglycemia mediated oxidative stress and apoptotic events in High fat and High fructose diet fed adult rats

2020 ◽  
Vol 11 (2) ◽  
pp. 1526-1538
Author(s):  
Porkodi Karthikeyan ◽  
Lakshmi Narasimhan Chakrapani ◽  
Thangarajeswari Mohan ◽  
Bhavani Tamilarasan ◽  
Pughazhendi Kannan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Diabetic Rats ◽  
High Fat ◽  
Gymnemic Acid ◽  
High Fructose ◽  
Type 2 Diabetic

Type 2 diabetes is delineated by impaired metabolic flexibility, and intramyocellular lipid accumulation, causing insulin resistance, particularly in skeletal muscle by reducing insulin-stimulated glucose uptake. High-fat diet and high fructose (HFD and HF) administration in rodents bestows a model for hyperlipidemia, insulin resistance, and Type 2 diabetes. The current study is focused on elucidating the role of Gymnemic acid in combating hyperglycemia mediated oxidative stress and apoptotic events in the skeletal muscle of HFD and HF induced Type 2 diabetes in Wistar albino rats by boosting antioxidant defense system. Gymnemic acid, a saponin of triterpene glycoside contained in leaves of Gymnema Sylvestre, has potent anti-diabetic properties. Treatment with Gymnemic acid restored the antioxidant status (Gpx, SOD, CAT, GR, Vit C & Vit E) with significant (p<0.05) decrease in free radical levels and reinvigorated the expression of apoptotic and antiapoptotic proteins in Type 2 diabetic rats. Histopathological data demonstrate that oral administration of Gymnemic acid protects skeletal muscle fibers from an oxidative niche in HFD and HF in Type 2 diabetic rats. In accordance with this, Gymnemic acid might be regarded as a promising therapeutic agent against Type 2 diabetes, thereby restoring skeletal muscle integrity and function.

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