The role of uncoupling protein 2 in the development of type 2 diabetes

2003 ◽  
Vol 39 (4) ◽  
pp. 287 ◽  
Author(s):  
D. Langin
Keyword(s):  
Type 2 Diabetes ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2

scholarly journals The role of uncoupling protein 2 (UCP2) on the development of type 2 diabetes mellitus and its chronic complications

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 ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Acid Metabolism ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Chronic Complications ◽  
Ucp2 Gene

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.

scholarly journals Association Study of Candidate Gene Uncoupling Protein 2 (UCP2) with Type 2 Diabetes Mellitus in the Different Population Groups of Jammu Region

2019 ◽  
Vol 16 (2) ◽  
pp. 351-357
Author(s):  
Sunil Raina ◽  
Roopali Fotra
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Disorders ◽  
Uncoupling Protein ◽  
Molecular Genetic ◽  
Promoter Polymorphism ◽  
Uncoupling Protein 2 ◽  
Population Groups ◽  
Allelic Odds Ratio

Diabetes Mellitus is a group of metabolic disorders characterized by hyperglycaemic resulting from the defects of insulin secretion, insulin action or both. The present study was conducted in order to know the molecular genetic cause of the T2DM patients belonging to the Jammu region of J&K State. Many genes have been known to be linked with the onset and progression of the T2DM therefore the present data represents the role of one of the genes Uncoupling protein 2 (UCP2) known to be strongly associated with T2DM was selected. A total of 250 confirmed cases & controls samples belonging to four population groups (Hindu, Muslim, Sikh & Christians) of Jammu region were also screened for UCP2 -866G/A promoter polymorphism (rs659366). The allelic odds ratio (OR) as observed for UCP2 -866G/A polymorphism in the four population groups showed significant association with Muslim & Sikh population groups. The study undertaken supports the findings of the previous investigations and thus is an addition to the existing literatute in support of UCP2 and T2DM.

scholarly journals Association of 45-bp ins/del polymorphism of uncoupling protein 2 (UCP2) and susceptibility to nonalcoholic fatty liver and type 2 diabetes mellitus in North-west of Iran

2020 ◽  
Author(s):  
Salehe Rezapour ◽  
Shiva Ahdi Khosroshahi ◽  
Hadi Farajnia ◽  
Fatemeh Mohseni ◽  
Manouchehr Khoshbaten ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Fatty Liver ◽  
Uncoupling Protein ◽  
P Value ◽  
Uncoupling Protein 2 ◽  
Genotype Distribution ◽  
Healthy Controls

Abstract Objective: Uncoupling protein 2 (UCP2) plays a crucial role in energy homeostasis via regulation of insulin secretion, free fatty acid concentrations, and lipid metabolism. This study aimed to investigate the association of 45-bp ins/del polymorphism of UCP2 with susceptibility to NAFLD (Non Alcoholic Fatty Liver Disease) and T2DM (Type 2 Diabetes Mellitus). DNA was extracted from the white blood cells of the subjects, and the gene polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In this study, 72 patients with NAFLD, 71 healthy individuals as control, 80 patients with T2DM, and 77 healthy controls were enrolled in the study.Results: A higher prevalence of insertion/insertion genotype was observed in T2DM patients compared to the controls (p- value˂ 0.05). But, there was no difference in genotype distribution between NAFLD patients and controls (p-value> 0.05). NAFLD patients with D/D, D/I genotype had higher triglyceride, ALT, and AST levels; however, their HDL levels were lower than healthy controls. Patients with T2DM with D/D or D/I genotype also had significantly higher fasting serum glucose (FSG). While we found an association between the 45bp I/D polymorphism in 3ʹUTR of UCP2 and T2DM, no any correlation between this polymorphism and NAFLD was identified.

Targeting PLD2 in adipocytes augments adaptive thermogenesis by improving mitochondrial quality and quantity in mice

2021 ◽  
Vol 219 (2) ◽  
Author(s):  
Hyung Sik Kim ◽  
Min Young Park ◽  
Nam Joo Yun ◽  
Hye Sun Go ◽  
Mi Young Kim ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Specific Inhibitor ◽  
Adaptive Thermogenesis ◽  
Diet Induced Obesity ◽  
Diet Induced Thermogenesis ◽  
And Migration

Phospholipase D (PLD)2 via its enzymatic activity regulates cell proliferation and migration and thus is implicated in cancer. However, the role of PLD2 in obesity and type 2 diabetes has not previously been investigated. Here, we show that during diet-induced thermogenesis and obesity, levels of PLD2 but not PLD1 in adipose tissue are inversely related with uncoupling protein 1, a key thermogenic protein. We demonstrate that the thermogenic program in adipose tissue is significantly augmented in mice with adipocyte-specific Pld2 deletion or treated with a PLD2-specific inhibitor and that these mice are resistant to high fat diet–induced obesity, glucose intolerance, and insulin resistance. Mechanistically, we show that Pld2 deletion in adipose tissue or PLD2 pharmacoinhibition acts via p62 to improve mitochondrial quality and quantity in adipocytes. Thus, PLD2 inhibition is an attractive therapeutic approach for obesity and type 2 diabetes by resolving defects in diet-induced thermogenesis.

scholarly journals The -866A/A Genotype in the Promoter of the Human Uncoupling Protein 2 Gene Is Associated With Insulin Resistance and Increased Risk of Type 2 Diabetes

Diabetes ◽  
2004 ◽  
Vol 53 (7) ◽  
pp. 1905-1910 ◽  
Author(s):  
M. D'Adamo ◽  
L. Perego ◽  
M. Cardellini ◽  
M. A. Marini ◽  
S. Frontoni ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Increased Risk

Uncoupling protein-2 polymorphisms in type 2 diabetes, obesity, and insulin secretion

2004 ◽  
Vol 286 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
Hua Wang ◽  
Winston S. Chu ◽  
Tong Lu ◽  
Sandra J. Hasstedt ◽  
Philip A. Kern ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Mrna Levels ◽  
Metabolic Study ◽  
Β Cell ◽  
Family Based ◽  
Ucp2 Mrna

The onset of type 2 diabetes (T2DM) is preceded by obesity, insulin resistance, and impaired β-cell function. Uncoupling protein-2 (UCP2) is a widely expressed inner mitochondrial membrane protein. Common polymorphisms of the UCP2 gene have been implicated in diabetes, in obesity, and with changes in UCP2 mRNA levels. We tested the hypothesis that common UCP2 variants influence T2DM susceptibility in four parallel studies of separate populations. We typed the -866 promoter (G/A) variant, a nonsynonymous (Ala55Val or A55V) single-nucleotide polymorphism in exon 4, and a 45-nt insertion in the 3′-untranslated (3′UTR) region. Study populations included a case-control population study, a family-based association study, and a metabolic study of individuals who had been characterized for insulin sensitivity and secretion. To evaluate UCP2 mRNA levels, we examined a fourth population of subjects, who had undergone subcutaneous fat biopsy. All three variants showed a trend to an association with T2DM ( P = 0.05 to 0.07) in the population but not the family-based association study. The 3′ insertion/deletion (3′UTR I/D) variant was associated with body mass index (BMI, P = 0.035) among nondiabetic family members. Haplotype combinations were significantly associated with BMI ( P = 0.028), triglyceride levels ( P = 0.026), and fasting insulin ( P = 0.029); highest values for the three traits were observed in individuals with the heterozygous combination GVI/AVD. In the metabolic study, all three variants were associated with an index of β-cell compensation for insulin sensitivity (disposition index), particularly in interaction with family membership ( P < 0.000001). Individuals homozygous for the -866 A allele had decreased adipose mRNA levels relative to GG homozygous individuals ( P = 0.009), but the 3′UTR I/D variant had no impact on mRNA levels. We confirm modest effects of UCP2 variants on BMI and T2DM and show significant effects on insulin secretion in interaction with family-specific factors. However, the associated allele and the effects on gene expression are opposite to those reported previously.

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 ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Uncoupling Protein 1 ◽  
Exon 2 ◽  
Brown Adipose

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.

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