Association of pyruvate dehydrogenase kinase 4 gene polymorphisms with type 2 diabetes and metabolic syndrome

2012 ◽  
Vol 95 (2) ◽  
pp. 230-236 ◽  
Author(s):  
Seong-Su Moon ◽  
Jung-Eun Lee ◽  
Young-Sil Lee ◽  
Su-Won Kim ◽  
Nam Ho Jeoung ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Pyruvate Dehydrogenase ◽  
Gene Polymorphisms ◽  
Pyruvate Dehydrogenase Kinase ◽  
Pyruvate Dehydrogenase Kinase 4

Vitamin D Receptor Gene Polymorphisms, Metabolic Syndrome, and Type 2 Diabetes in Iranian Subjects: No Association with Observed SNPs

2016 ◽  
Vol 86 (1-2) ◽  
pp. 71-80 ◽  
Author(s):  
Sakineh Shab-Bidar ◽  
Tirang R. Neyestani ◽  
Abolghassem Djazayery
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Gene Polymorphisms ◽  
Receptor Gene ◽  
Vitamin D Receptor Gene ◽  
Single Nucleotide ◽  
Receptor Gene Polymorphisms

Abstract.Objective: This study aimed to investigate the associations between metabolic syndrome and type 2 diabetes and the presence of single nucleotide polymorphism of the vitamin D receptor gene in Iranian subjects with type 2 diabetes. Subjects and methods: Overall, 730 Iranian subjects (372 patients and 358 controls) were enrolled in this case-control study. Single nucleotide polymorphisms of the vitamin D receptor gene (FokI, BsmI, ApaI, and TaqI) were genotyped using the restriction fragment length polymorphism method. The statistical difference in genotype distribution among the groups was assessed by χ2 test. Logistic regression was performed to calculate odds ratios for the association of the genotype frequencies in different groups with the risk of metabolic syndrome and type 2 diabetes. Results: The most common genotypes for BsmI, ApaI, TaqI, and FokI were Bb, Aa, TT, and FF, respectively. Adjusted χ2 test revealed that there was no difference between the groups in the genotypes frequencies of 4 vitamin D receptor polymorphisms in type 2 diabetes subjects. On the other hand, type 2 diabetes subjects with Tt genotype presented a signifi cantly higher fasting blood glucose than those with TT and tt genotypes in TaqI polymorphisms (p = 0.009). Logistic regression showed no association between metabolic syndrome risk and vitamin D receptor genotypes. Conclusion: We found no evidence for the association between vitamin D receptor gene polymorphisms and the risk for type 2 diabetes and metabolic syndrome in Iranian subjects. Further examinations using genome-wide association in large prospective cohort studies are warranted.

Association of HSD11B1 gene polymorphisms with type 2 diabetes and metabolic syndrome in South Indian population

2017 ◽  
Vol 131 ◽  
pp. 142-148 ◽  
Author(s):  
Nayana Devang ◽  
Kapaettu Satyamoorthy ◽  
Padmalatha S. Rai ◽  
M. Nandini ◽  
Satish Rao ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Gene Polymorphisms ◽  
Indian Population ◽  
South Indian Population ◽  
South Indian

scholarly journals The Effect of Various Fatty Acids on Activity of G6pase-A and Pdk4 in Hepg2 CellA

2019 ◽  
pp. 1-6
Author(s):  
Lisa Maness ◽  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Increase Insulin Sensitivity ◽  
Beneficial Effects ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
Arachidonic Acids

Aims: The current study aimed to determine the effects of various fatty acids on the expression of glucose-6-phosphatase-α (G6Pase-α) and pyruvate dehydrogenase kinase 4 (PDK4). Methods: HepG2 cells were seeded in a 96-well plate with Dulbecco’s Modified Eagle Media, high glucose and bovine serum albumin with 25 µmoll of each fatty acid individually (butyric, politic, stearic, oleic, linoleic, linolenic, and arachidonic acids) for 24 hours at 37°C with and without 10 minute incubation of 100 nmol insulin. qPCR was performed using G6Pase-α and PDK4 primers; fold-changes in gene activity were determined. Results: Butyric (-2.0) and linoleic (-65.8) acids caused down regulations of G6Pase-α in the presence of insulin while linoleic (-96.6) acid caused a down regulation of PDK4 in the presence of insulin; all caused upregulations of both these genes in the absence of insulin. Conclusions: This study suggests that linolenic acid, which is present in soybeans, walnuts, and kiwi seeds, is beneficial to processing glucose and could increase insulin sensitivity through molecular influence in patients with metabolic syndrome or serve as prevention. Other fatty acids tested, with exception of butyric acid, did not show beneficial effects in the direction of decreasing glucose

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 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.

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