Uncoupling protein 3 is reduced in skeletal muscle of NIDDM patients.

Krook, Anna; Digby, J; O’Rahilly, Stephen; Zierath, Juleen R.; Wallberg-Henriksson, Harriet

doi:10.2337/diabetes.47.9.1528

Cited by 99 publications

(86 citation statements)

References 23 publications

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“…El alelo -55C de UCP3 podría tener un papel funcional, dado que se ha asociado con una menor cantidad de ARNm y de proteína en músculo esquelético (43,44).…”

Section: Discussionunclassified

Asociación de variantes en genes de las proteínas desacoplantes con diabetes mellitus tipo 2 en una población del nordeste colombiano

et al. 2009

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Introducción. Las proteínas desacoplantes pertenecen a la familia de proteínas transportadoras de aniones que desacoplan la producción de ATP de la respiración mitocondrial, causando pérdida de protones a través de la membrana mitocondrial interna y disipando la energía en forma de calor. Aunque su función no ha sido bien establecida, algunos polimorfismos en estas proteínas se han asociado con diabetes mellitus tipo 2, obesidad y resistencia a la insulina. Objetivo. Evaluar la asociación entre las variantes -3826A/G, ID 45, -2723T/A, -1957G/A, -866G/A, -55C/T de los genes de las proteínas desacoplantes 1, 2 y 3 con diabetes mellitus tipo 2 en una población del nordeste colombiano. Materiales y métodos. Se tipificaron 545 casos y 449 controles para 14 variantes de los genes de las proteínas desacoplantes por medio de PCR y PCR-RFLP. Se hicieron pruebas de asociación simples con ji al cuadrado y se corrigieron en un análisis de regresión logística bayesiana, incluyendo los estimados de mezcla individual obtenidos mediante 54 marcadores informativos de ascendencia europea, africana y amerindia. Resultados. Las variantes -3826A (OR=0,78; IC95% 0,63-0,97; p=0,02), -55C (OR=1,41; IC95% 1,04-1,92; p=0,03) de las proteínas desacoplantes 1 y 3, respectivamente, y el haplotipo D45, -866G, -1957G, -2723T, -55C (OR=1,26; IC95% 1,02-1,56; p=0,03) se asociaron con diabetes tipo 2. Estas asociaciones se conservaron después de ajustar por la mezcla genética individual. Conclusión. Algunas variantes de las proteínas desacoplantes 1, 2 y 3, y sus haplotipos, confieren riesgo para diabetes mellitus tipo 2 en una población del nordeste colombiano.Palabras clave: diabetes mellitus/genética, resistencia a insulina, obesidad, genotipo, haplotipos. Association between polymorphism in uncoupling proteins and type 2 diabetes in a northwestern Colombian populationIntroduction. The uncoupling proteins belong to the family of anion transporting proteins which uncouple the ATP production from the mitochondrial respiration, cause proton leakage through the inner mitochondrial membrane, and release energy as heat. Although uncoupling protein function has not been well established, specific polymorphisms in these proteins have been associated with type 2 diabetes mellitus, obesity and insulin resistance. Objective. The association was assessed between the polymorphisms in uncoupling protein genes 1, 2 and 3 genes and type 2 diabetes mellitus. Materials and methods. In a northwestern Colombian population, 545 diabetes cases and 449 controls were investigated for presence of 14 polymorphisms in uncoupling protein genes (3826A/G, ID 45, 2723T/A, 1957G/A, 866G/A, and 55C/T) by PCR and PCR-RFLP. Single associations were evaluated by chi-square test, and bayesian logistic regression analysis was done including as covariates the individual admixture estimates obtained by 54 D45, 866G, 1957G, 2723T, and 55C (OR=1.26; 95%CI=1.02-1.56; p=0.03) were found. These associations remained after adjustment using individual genetic admixture estimates. Concl...

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“…El alelo -55C de UCP3 podría tener un papel funcional, dado que se ha asociado con una menor cantidad de ARNm y de proteína en músculo esquelético (43,44).…”

Section: Discussionunclassified

Asociación de variantes en genes de las proteínas desacoplantes con diabetes mellitus tipo 2 en una población del nordeste colombiano

et al. 2009

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“…Although a direct role of UCP2 in Type II diabetes seems unlikely, based on the genetic data, it is still conceivable that in some ethnic groups variants of UCP3 possibly contribute to the pathogenesis of Type II diabetes. Indeed, mRNA levels of UCP3 have been found to be considerably reduced in skeletal muscle of Type II diabetic patients compared with control subjects [29].…”

Section: Discussionmentioning

confidence: 99%

An uncoupling protein 2 gene variant is associated with a raised body mass index but not Type II diabetes

et al. 1999

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The regulation of body fat equilibrium in mammals depends on a balance between diet and energy expenditure. Energy expenditure occurs as a result of a combination of resting metabolic rate, physical exercise and non-shivering thermogenesis. It has become increasingly evident that even small calorific inequalities can lead to an increase in fat storage and obesity. There is also an intimate association between increasing body weight and Type II (non-insulin-dependent) diabetes even in populations in which obesity is not a common problem. The recent addition of two new uncoupling proteins (UCP), UCP2 and UCP3 to the mitochondrial carrier protein family of genes provides new opportunities to study thermogenesis in humans [1±3]. Activated uncoupling proteins promote proton transport and consequently decrease the proton electrochemical potential gradient across the inner mitochondrial membrane. This uncouples oxidative phosphorylation of ADP to ATP, leading to generation of heat [4]. A close relation between obesity in mice Diabetologia (1999) AbstractAims/hypothesis. Linkage between markers close to the uncoupling protein 2 and 3 genes (11q13) and resting metabolic rate and a pre-diabetic phenotype have been found. The syntenic region in mouse has been found to be linked to quantitative traits associated with obesity and diabetes. UCP2 and UCP3 could therefore have an important role in body weight regulation and susceptibility to diabetes. We investigated a recently identified variant of the UCP2 gene in exon 8 as a marker for glucose and weight homeostasis. Methods. Length variation of the UCP2 exon 8 variant was studied by the polymerase chain reaction and agarose gel electrophoresis. Sequence variants of the UCP3 gene were sought by semi-automated DNA sequencing. Results. In 453 South Indian subjects, we found an association in women between the UCP2 exon variant and body mass index (p = 0.018). These findings were replicated in a separate group of South Indian subjects (n = 143, p < 0.001) irrespective of sex. Although no association was found between the UCP2 exon 8 variant and overt obesity in British subjects, the UCP2 genotype of obese women (n = 83) correlated with fasting serum leptin concentration (p = 0.006) in the presence of extreme obesity. These observations could not be explained by tight linkage disequilibrium with a coding region variant in the region of the UCP3 gene of biological significance. Lastly, no association was found between UCP2 and Type II (non-insulin-dependent) diabetes using either a family based design (85 families) or case control study (normal glucose tolerance n = 335, impaired glucose tolerance n = 42, Type II diabetes n = 76). Conclusion/interpretation. We have described a UCP2 gene exon 8 variant that may affect susceptibility to weight gain by influencing regulation of leptin. [Diabetologia (1999) 42: 688±693]

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“…Two groups reported the detection of UCP2 in human skeletal muscle using Western analysis with antibodies directed either against the N-terminal [75] or the C-terminal [76] extremity of the protein, although the identity of the antigen was not proven. A description of an UCP2 antigen in Western analysis of rat white adipose tissue was not entirely convincing, since the authors utilized an antiserum against UCP1 and since white fat contains …”

Section: Immunological Detection Of Ucpsmentioning

confidence: 99%

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

Ricquier¹,

Bouillaud

2000

Biochemical Journal

610

115

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Animal and plant uncoupling protein (UCP) homologues form a subfamily of mitochondrial carriers that are evolutionarily related and possibly derived from a proton\anion transporter ancestor. The brown adipose tissue (BAT) UCP1 has a marked and strongly regulated uncoupling activity, essential to the maintenance of body temperature in small mammals. UCP homologues identified in plants are induced in a cold environment and may be involved in resistance to chilling. The biochemical activities and biological functions of the recently identified mammalian UCP2 and UCP3 are not well known. However, recent data support a role for these UCPs in State 4 respiration, respiration uncoupling and proton leaks in mitochondria. Moreover, genetic studies suggest that UCP2 and UCP3 play a part in

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Uncoupling protein 3 is reduced in skeletal muscle of NIDDM patients.

Cited by 99 publications

References 23 publications

Asociación de variantes en genes de las proteínas desacoplantes con diabetes mellitus tipo 2 en una población del nordeste colombiano

Asociación de variantes en genes de las proteínas desacoplantes con diabetes mellitus tipo 2 en una población del nordeste colombiano

An uncoupling protein 2 gene variant is associated with a raised body mass index but not Type II diabetes

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

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