scholarly journals The role of the uncoupling protein 1 (UCP1) on the development of obesity and type 2 diabetes mellitus

2012 ◽  
Vol 56 (4) ◽  
pp. 215-225 ◽  
Author(s):  
Letícia de Almeida Brondani ◽  
Taís Silveira Assmann ◽  
Guilherme Coutinho Kullmann Duarte ◽  
Jorge Luiz Gross ◽  
Luís Henrique Canani ◽  
...  

It is well established that genetic factors play an important role in the development of both type 2 diabetes mellitus (DM2) and obesity, and that genetically susceptible subjects can develop these metabolic diseases after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2 and/or obesity. Uncoupling protein 1 (UCP1) is mainly expressed in brown adipose tissue, and acts in thermogenesis, regulation of energy expenditure, and protection against oxidative stress. All these mechanisms are associated with the pathogenesis of DM2 and obesity. Hence, UCP1 is a candidate gene for the development of these disorders. Indeed, several studies have reported that polymorphisms -3826A/G, -1766A/G and -112A/C in the promoter region, Ala64Thr in exon 2 and Met299Leu in exon 5 of UCP1 gene are possibly associated with obesity and/or DM2. However, results are still controversial in different populations. Thus, the aim of this study was to review the role of UCP1 in the development of these metabolic diseases.

2021 ◽  
Vol 59 (5) ◽  
pp. 599-607
Author(s):  
O. V. Zhelyabina ◽  
M. S. Eliseev

Gout is the most common inflammatory arthritis in adults and has continued to increase in prevalence over the past decades. Gout is characterized by hyperuricemia with the obligatory crystallization of urates and an associated inflammatory reaction, as well as metabolic effects caused, among other things, by these processes. In particular, the diagnosis of gout is identified with a high risk of carbohydrate metabolism disorders, which is 2 times higher than the population risk: according to various sources, from 21 to 26% of patients with gout have type 2 diabetes mellitus (DM 2). However, the role of uric acid and urate-lowering drugs in its development in patients with gout remains controversial. The possibility of influencing the risk of developing diabetes mellitus type 2 of chronic inflammation, the activity of interleukin-1β and other pro-inflammatory cytokines, hyperuricemia, xanthioxidase and other factors associated with gout is discussed. It is possible that the level of uric acid is associated with diabetes and other metabolic diseases, causing pathophysiological changes not only through inflammation, but also oxidative stress, damage to the vascular endothelium. It is also suggested that gout and DM 2 may share genetic markers. The interrelation of violations of purine and carbohydrate metabolism prompts the search for drugs that have a simultaneous positive effect on purine and carbohydrate metabolism. However, it is not clear what the level of uric acid should be considered as a risk factor, there are conflicting data on the possibility of reducing the risk of developing diabetes with various anti-gout therapies.


2011 ◽  
Vol 55 (4) ◽  
pp. 239-248 ◽  
Author(s):  
Bianca Marmontel de Souza ◽  
Taís Silveira Assmann ◽  
Lúcia Maria Kliemann ◽  
Jorge Luiz Gross ◽  
Luís Henrique Canani ◽  
...  

It is well established that genetic factors play an important role in the development of type 2 diabetes mellitus (DM2) and its chronic complications, and that genetically susceptible subjects can develop the disease after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2. Uncoupling protein 2 (UCP2) is expressed in several tissues, and acts in the protection against oxidative stress; in the negative regulation of insulin secretion by beta cells, and in fatty acid metabolism. All these mechanisms are associated with DM2 pathogenesis and its chronic complications. Therefore, UCP2 is a candidate gene for the development of these disorders. Indeed, several studies have reported that three common polymorphisms in UCP2 gene are possibly associated with DM2 and/or obesity. Only a few studies investigated these polymorphisms in relation to chronic complications of diabetes, with inconclusive results.


Author(s):  
Nermien Abd El Rahman Ibraheim ◽  
Fatema El Zahraa Sayed Bukhary ◽  
Yehia Zakareia Mahmoud ◽  
Mahmoud Ragab Mohamed ◽  
Salama Rabei Abdel-Rahim

2020 ◽  
Vol 26 ◽  
Author(s):  
Margarita A. Sazonova ◽  
Anastasia I. Ryzhkova ◽  
Vasily V. Sinyov ◽  
Marina D. Sazonova ◽  
Tatiana V. Kirichenko ◽  
...  

Background: The present review article considers some chronic diseases of vascular and metabolic genesis, the causes of which may be mitochondrial dysfunction. Very often, in the long course of the disease, complications may occur, leading to myocardial infarction or ischemic stroke and as a result, death.In particular, a large percentage of human deaths nowadays belongs to cardiovascular diseases such as coronary heart disease (CHD), arterial hypertension, cardiomyopathies and type 2 diabetes mellitus. Objective: The aim of the present review was the analysis of literature sources, devoted to an investigation of a link of mitochondrial DNA mutations with chronic diseases of vascular and metabolic genesis, Results: The analysis of literature indicates the association of the mitochondrial genome mutations with coronary heart disease, type 2 diabetes mellitus, hypertension and various types of cardiomyopathies. Conclusion: The detected mutations can be used to analyze the predisposition to chronic diseases of vascular and metabolic genesis. They can also be used to create molecular-cell models necessary to evaluate the effectiveness of drugs developed for treatment of these pathologies. MtDNA mutations associated withthe absence of diseases of vascular and metabolic genesis could be potential candidates for gene therapy of diseases of vascular and metabolic genesis.


2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.


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