scholarly journals The Effect of Periodic Exercise and Resveratrol Supplementation on the Expression of Pparg Coactivator-1 Alpha and Pyruvate Dehydrogenase Kinase Genes in Gastrocnemius Muscle of Old Rats With Type 2 Diabetes

2020 ◽  
Vol 26 (1) ◽  
pp. 68-81
Author(s):  
Ali Salehi ◽  
◽  
Hajar Abbaszadeh ◽  
Parvin Farzanegi ◽  
◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Pyruvate Dehydrogenase ◽  
Gastrocnemius Muscle ◽  
Diabetic Control ◽  
Pyruvate Dehydrogenase Kinase ◽  
Male Rats ◽  
Expression Levels ◽  
Old Rats

Aims: Type 2 diabetes is the result of complex interactions between genetic and environmental factors that affect fat and glucose metabolism. The purpose of this study was to determine the effect of periodic exercise and resveratrol supplement on the expression levels of Pparg Coactivator 1-Alpha (PGC-1α) and Pyruvate Dehydrogenase Kinase (PDK4) genes in gastrocnemius muscle of old rates with type 2 diabetes. Methods & Materials: 42 male rats (mean age= 40-50 weeks; mean body weight= 250-300 g) were randomly divided into 6 groups: healthy-control, diabetic-control, Diabetic+Periodic Exercise, Diabetic+Supplement, Diabetic+Periodic Exercise+Supplement and Saline. The type 2 diabetes was induced by intraperitoneal injection of Streptozotocin (50 mg/kg body weight). The exercise protocol consisted of 10 sets of 1-min activities at 50% intensity and a 2-min rest period between sets, and each week the speed was increased by 2 meters per minute. The exercises were performed for eight weeks. Resveratrol supplement was injected intraperitoneally daily at a dose of 20 mg/kg body weight. The expressions of PDK4 and PGC-1α in the gastrocnemius muscle were measured by real time Polymerase Chain Reaction (PCR) method. Findings: highest expression level of PDK4 and PGC-1α genes in gastrocnemius muscle was observed in the diabetic group received both periodic exercise and Resveratrol supplement and the lowest level was reported in the diabetic-control and saline groups. Conclusion The combination of resveratrol supplementation and periodic exercise can have beneficial effects on PDK4 and PGC-1α expression levels in the gastrocnemius muscle of old rats with type 2 diabetes and reduce the risks of diabetes-related complications.

scholarly journals Beneficial Effects of Soygurt Intake in Type 2 Diabetes Mellitus in Animal Model Rat (Rattus Norvegitus)

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ni Wayan Desi Bintari ◽  
Putu Ayu Parwati
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Blood Sugar ◽  
Blood Sugar Level ◽  
Diabetic Rats ◽  
Male Rats ◽  
Probiotic Food

Type 2 Diabetes Mellitus (T2DM) is the more common type of diabetes results from the ineffective use of insulin. Improvement of the metabolic system in T2DM patients can be done through the regulation of gut microbiota balance. Gut microbial improvement can be modulated directly by probiotic food consumption. Soygurt is probiotic food with a low glycemic index (GI) and glycemic load (GL) value and rich in isoflavones, which has a potential effect in reducing diabetes risk. The aim of this study is to determine the effect of soygurt consumption in blood glucose levels and body weight of albino wistar rats (Rattus norvegitus). Reseach using a completely randomized design for experimental study. Subjects of this research are 30 male rats (R. norvegistus) aged 2-3 months with average body weight 150-200 gr. Diabetic rats were induced by using single intraperitoneal injection (175 mg/kg BW) alloxan monohydrate. Soygurt feeding given once daily using oral gavage feeding. The result showed that soygurt feeding in diabetic rats with three variations of treatment could significantly (p<0,05), lowering blood sugar level and improve body weight after 28 days of treatment. Treatment of 4ml/day soygurt has the highest effect in lowering blood sugar level and improving body weight, followed by treatment of 3ml/day and 2ml/day soygurt.

scholarly journals Interactions between PPAR Gamma and the Canonical Wnt/Beta-Catenin Pathway in Type 2 Diabetes and Colon Cancer

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yves Lecarpentier ◽  
Victor Claes ◽  
Alexandre Vallée ◽  
Jean-Louis Hébert
Keyword(s):  
Type 2 Diabetes ◽  
Colon Cancer ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Ppar Gamma ◽  
Pyruvate Dehydrogenase Kinase ◽  
Peroxisome Proliferator ◽  
Beta Catenin ◽  
Canonical Wnt

In both colon cancer and type 2 diabetes, metabolic changes induced by upregulation of the Wnt/beta-catenin signaling and downregulation of peroxisome proliferator-activated receptor gamma (PPAR gamma) may help account for the frequent association of these two diseases. In both diseases, PPAR gamma is downregulated while the canonical Wnt/beta-catenin pathway is upregulated. In colon cancer, upregulation of the canonical Wnt system induces activation of pyruvate dehydrogenase kinase and deactivation of the pyruvate dehydrogenase complex. As a result, a large part of cytosolic pyruvate is converted into lactate through activation of lactate dehydrogenase. Lactate is extruded out of the cell by means of activation of monocarboxylate lactate transporter-1. This phenomenon is called Warburg effect. PPAR gamma agonists induce beta-catenin inhibition, while inhibition of the canonical Wnt/beta-catenin pathway activates PPAR gamma.

AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2

2003 ◽  
Vol 31 (6) ◽  
pp. 1168-1170 ◽  
Author(s):  
J.A. Morrell ◽  
J. Orme ◽  
R.J. Butlin ◽  
T.E. Roche ◽  
R.M. Mayers ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Pyruvate Dehydrogenase ◽  
Kinase Inhibitors ◽  
Selective Inhibitor ◽  
Pyruvate Dehydrogenase Kinase ◽  
Enzyme Complex ◽  
Specific Expression ◽  
Related Compounds

The PDH (pyruvate dehydrogenase) multi-enzyme complex catalyses a key regulatory step in oxidative glycolysis. Phosphorylation of the E1 subunit of the complex on serine residues results in the inactivation of enzyme activity. A family of four dedicated PDH kinase isoenzymes exists, each of which displays a distinct tissue-specific expression profile. AZD7545 is one of a series of PDH kinase inhibitors developed for the treatment of type 2 diabetes. The isoenzyme-selectivity profile of AZD7545 and related compounds is described and the consequences for their in vivo mode of action are discussed.

Pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) deficiency attenuates the long-term negative effects of a high-saturated fat diet

2009 ◽  
Vol 423 (2) ◽  
pp. 243-252 ◽  
Author(s):  
Byounghoon Hwang ◽  
Nam Ho Jeoung ◽  
Robert A. Harris
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Blood Glucose ◽  
Knockout Mice ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Saturated Fat ◽  
Pyruvate Dehydrogenase Kinase ◽  
Wild Type

The hypothesis that PDHK4 (pyruvate dehydrogenase kinase isoenzyme 4) has potential as a target for the treatment of type 2 diabetes was tested by feeding wild-type and PDHK4 knockout mice a high saturated fat diet that induces hyperglycemia, hyperinsulinaemia, glucose intolerance, hepatic steatosis and obesity. Previous studies have shown that PDHK4 deficiency lowers blood glucose by limiting the supply of three carbon gluconeogenic substrates to the liver. There is concern, however, that the increase in glucose oxidation caused by less inhibition of the pyruvate dehydrogenase complex by phosphorylation will inhibit fatty acid oxidation, promote ectopic fat accumulation and worsen insulin sensitivity. This was examined by feeding wild-type and PDHK4 knockout mice a high saturated fat diet for 8 months. Fasting blood glucose levels increased gradually in both groups but remained significantly lower in the PDHK4 knockout mice. Hyperinsulinaemia developed in both groups, but glucose tolerance was better and body weight was lower in the PDHK4 knockout mice. At termination, less fat was present in the liver and skeletal muscle of the PDHK4 knockout mice. Higher amounts of PGC-1α [PPARγ (peroxisome proliferator-activated receptor γ) coactivator 1α] and PPARα and lower amounts of fatty acid synthase and acetyl-CoA carboxylase isoenzyme 1 were present in the liver of the PDHK4 knockout mice. These findings suggest PDHK4 deficiency creates conditions that alter upstream signalling components involved in the regulation of lipid metabolism. The findings support the hypothesis that PDHK4 is a viable target for the treatment of type 2 diabetes.

Impaired oxidative phosphorylation in skeletal muscle of intrauterine growth-retarded rats

2003 ◽  
Vol 285 (1) ◽  
pp. E130-E137 ◽  
Author(s):  
Mary A. Selak ◽  
Bayard T. Storey ◽  
Iyalla Peterside ◽  
Rebecca A. Simmons
Keyword(s):  
Type 2 Diabetes ◽  
Oxidative Phosphorylation ◽  
Growth Retardation ◽  
Pyruvate Dehydrogenase ◽  
Intrauterine Growth Retardation ◽  
Glycogen Synthesis ◽  
Later Life ◽  
Pyruvate Dehydrogenase Kinase ◽  
Intrauterine Growth

Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in later life. We have developed a model of uteroplacental insufficiency, a common cause of intrauterine growth retardation, in the rat. Early in life, the animals are insulin resistant and by 6 mo of age they develop diabetes. Glycogen content and insulin-stimulated 2-deoxyglucose uptake were significantly decreased in muscle from IUGR rats. IUGR muscle mitochondria exhibited significantly decreased rates of state 3 oxygen consumption with pyruvate, glutamate, α-ketoglutarate, and succinate. Decreased pyruvate oxidation in IUGR mitochondria was associated with decreased ATP production, decreased pyruvate dehydrogenase activity, and increased expression of pyruvate dehydrogenase kinase 4. Such a defect in IUGR mitochondria leads to a chronic reduction in the supply of ATP available from oxidative phosphorylation. Impaired ATP synthesis in muscle compromises energy-dependent GLUT4 recruitment to the cell surface, glucose transport, and glycogen synthesis, which contribute to insulin resistance and hyperglycemia of type 2 diabetes.

scholarly journals Combined Administration of Streptozotocin and Sucrose Accelerates the Appearance of Type 2 Diabetes Symptoms in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Martha Isela Barragán-Bonilla ◽  
Juan Miguel Mendoza-Bello ◽  
Penélope Aguilera ◽  
Isela Parra-Rojas ◽  
Berenice Illades-Aguiar ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Fasting Blood Glucose ◽  
Signs And Symptoms ◽  
Male Rats ◽  
Oral Glucose ◽  
Chronic Hyperglycemia ◽  
Insulin Tolerance ◽  
Female Wistar Rats

Type 2 diabetes is a disease with a high global prevalence, characterized by chronic hyperglycemia, insulin resistance, polyphagia, polydipsia, polyuria, and changes in body weight. Animal models have been very useful for the study of this disease and to search for new therapeutic targets that delay, attenuate, or avoid diabetic complications. The purpose of this work was to establish a model of type 2 diabetes and exhibit the majority of the characteristics of the disease. Two-day-old male and female Wistar rats were treated once with streptozotocin (70 or 90 mg/kg body weight). After weaning, they were given a sucrose-sweetened beverage (SSB; sucrose at 10 or 30%) during 7 or 11 weeks; their body weight and food intake were measured daily. With the rats at 14 weeks of age, we determined the following: (a) fasting blood glucose, (b) oral glucose tolerance, and (c) insulin tolerance. We found that the supplementation of sucrose at 10% for 7 weeks in male rats which had previously been given streptozotocin (70 mg/kg) at neonatal stage leads to the appearance of the signs and symptoms of the characteristic of type 2 diabetes in adulthood.

How to Maintain a Healthy Body Weight

2006 ◽  
Vol 76 (4) ◽  
pp. 208-215 ◽  
Author(s):  
Astrup
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Body Weight ◽  
Glycemic Index ◽  
Dairy Products ◽  
Weight Control ◽  
Healthy Body Weight ◽  
Healthy Body

The epidemic of both obesity and type 2 diabetes is due to environmental factors, but the individuals developing the conditions possess a strong genetic predisposition. Observational surveys and intervention studies have shown that excess body fatness is the major environmental cause of type 2 diabetes, and that even a minor weight loss can prevent its development in high-risk subjects. Maintenance of a healthy body weight in susceptible individuals requires 45–60 minutes physical activity daily, a fat-reduced diet with plenty of fruit, vegetables, whole grain, and lean meat and dairy products, and moderate consumption of calorie containing beverages. The use of table values to predict the glycemic index of meals is of little – if any – value, and the role of a low-glycemic index diet for body weight control is controversial. The replacement of starchy carbohydrates with protein from lean meat and lean dairy products enhances satiety, and facilitate weight control. It is possible that dairy calcium also promotes weight loss, although the mechanism of action remains unclear. A weight loss of 5–10% can be induced in almost all obese patients providing treatment is offered by a professional team consisting of a physician and dieticians or nurses trained to focus on weight loss and maintenance. Whereas increasing daily physical activity and regular exercise does not significantly effect the rate of weight loss in the induction phase, it plays an important role in the weight maintenance phase due to an impact on daily energy expenditure and also to a direct enhancement of insulin sensitivity.

Clinical Experience with Insulin Detemir: Results from the Bangladesh Cohort of Global A1chieve Study

2013 ◽  
Vol 3 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Zafar Ahmed Latif ◽  
Md. Faruque Pathan ◽  
Md. Nazrul Islam Siddiqui ◽  
MA Mannan ◽  
SM Ashrafuzzaman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Glycaemic Control ◽  
Insulin Therapy ◽  
Hba1c Level ◽  
Insulin Detemir ◽  
Entire Cohort ◽  
Baseline Visit ◽  
Effective Option

Objective: To present results from the Bangladesh cohort of the A1chieve study receiving insulin detemir (Levemir) ± oral anti diabetic drugs. Methods: Out of 1093 patients recruited from 49 sites in Bangladesh, 370 were initiated on insulin detemir (Levemir).Study visits were defined as baseline, interim (around 12 weeks from baseline) and final (around 24 weeks from baseline) visit. Results: Glycaemic control was poor in all the groups at baseline. In the entire cohort at 24 weeks, significant reductions from baseline were observed in mean HbA1c (from 10.0 % to 7.2%, p<0.001), FPG (from 10.5 to 6.7 mmol/L, p<0.001) and PPPG (from 15.3 to 8.9 mmol/L, p<0.001) levels. Overall 45.5% of the participants achieved target HbA1c level of < 7% after 24 weeks. The rate of all hypoglycaemic events in the entire cohort reduced from 1.34 (baseline) to 0.12 events/person year after 24 weeks of insulin detemir therapy (p<0.0001). There was no clinically relevant change in body weight in insulin naïve or prior insulin users groups after 24 weeks of insulin detemir therapy. Conclusions: The current study suggests that insulin detemir may be considered as a safe and effective option for initiating insulin therapy for type 2 diabetes in Bangladesh. Birdem Med J 2013; 3(1): 11-18 DOI: http://dx.doi.org/10.3329/birdem.v3i1.17121

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