A novel missense mutation, R70W, in the human uncoupling protein 3 gene in a family with type 2 diabetes

1999 ◽  
Vol 13 (6) ◽  
pp. 506-506 ◽  
Author(s):  
A.M. Brown ◽  
S.M. Willi ◽  
G. Argyropoulos ◽  
W.T. Garvey
Keyword(s):  
Type 2 Diabetes ◽  
Missense Mutation ◽  
Uncoupling Protein ◽  
Uncoupling Protein 3

scholarly journals Uncoupling Protein 3 Content Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes

Diabetes ◽  
2001 ◽  
Vol 50 (12) ◽  
pp. 2870-2873 ◽  
Author(s):  
P. Schrauwen ◽  
M. K.C. Hesselink ◽  
E. E. Blaak ◽  
L. B. Borghouts ◽  
G. Schaart ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Uncoupling Protein ◽  
Uncoupling Protein 3

A novel missense mutation in ADRB3 increases risk for type 2 diabetes in a Mexican American family

2006 ◽  
Vol 22 (4) ◽  
pp. 331-336 ◽  
Author(s):  
Donna M. Lehman ◽  
Jeanette Hamlington ◽  
Kelly J. Hunt ◽  
Robin J. Leach ◽  
Rector Arya ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Missense Mutation ◽  
Mexican American ◽  
American Family ◽  
Mexican American Family

scholarly journals A Missense Mutation of Pax4 Gene (R121W) Is Associated With Type 2 Diabetes in Japanese

Diabetes ◽  
2001 ◽  
Vol 50 (12) ◽  
pp. 2864-2869 ◽  
Author(s):  
Y. Shimajiri ◽  
T. Sanke ◽  
H. Furuta ◽  
T. Hanabusa ◽  
T. Nakagawa ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Missense Mutation

scholarly journals SNPs for Genes Encoding the Mitochondrial Proteins Sirtuin3 and Uncoupling Protein 2 Are Associated With Disease Severity, Type 2 Diabetes, and Outcomes in Patients With Pulmonary Arterial Hypertension and This Is Recapitulated in a New Mouse Model Lacking Both Genes

2021 ◽  
Author(s):  
Yongneng Zhang ◽  
Sotirios D. Zervopoulos ◽  
Aristeidis E. Boukouris ◽  
Maria Areli Lorenzana‐Carrillo ◽  
Bruno Saleme ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Pulmonary Arterial Hypertension ◽  
Mouse Model ◽  
Pulmonary Artery ◽  
Uncoupling Protein ◽  
Wild Type ◽  
Double Knockout ◽  
Pulmonary Arterial

Background Isolated loss‐of‐function single nucleotide polymorphisms (SNPs) for SIRT3 (a mitochondrial deacetylase) and UCP2 (an atypical uncoupling protein enabling mitochondrial calcium entry) have been associated with both pulmonary arterial hypertension (PAH) and insulin resistance, but their collective role in animal models and patients is unknown. Methods and Results In a prospective cohort of patients with PAH (n=60), we measured SNPs for both SIRT3 and UCP2, along with several clinical features (including invasive hemodynamic data) and outcomes. We found SIRT3 and UCP2 SNPs often both in the same patient in a homozygous or heterozygous manner, correlating positively with PAH severity and associated with the presence of type 2 diabetes and 10‐year outcomes (death and transplantation). To explore this mechanistically, we generated double knockout mice for Sirt3 and Ucp2 and found increasing severity of PAH (mean pulmonary artery pressure, right ventricular hypertrophy/dilatation and extensive vascular remodeling, including inflammatory plexogenic lesions, in a gene dose‐dependent manner), along with insulin resistance, compared with wild‐type mice. The suppressed mitochondrial function (decreased respiration, increased mitochondrial membrane potential) in the double knockout pulmonary artery smooth muscle cells was associated with apoptosis resistance and increased proliferation, compared with wild‐type mice. Conclusions Our work supports the metabolic theory of PAH and shows that these mice exhibit spontaneous severe PAH (without environmental or chemical triggers) that mimics human PAH and may explain the findings in our patient cohort. Our study offers a new mouse model of PAH, with several features of human disease that are typically absent in other PAH mouse models.

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.

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