The uncoupling protein 1 gene, UCP1, is expressed in mammalian islet cells and associated with acute insulin response to glucose in African American families from the IRAS Family Study

Sale, Michèle M.; Hsu, Fang‐Chi; Palmer, Nicholette D.; Gordon, Candace J.; Keene, Keith L.; Borgerink, Hermina; Sharma, Arun; Bergman, Richard N.; Taylor, Kent D.; Saad, Mohammed F.; Norris, Jill M.

doi:10.1186/1472-6823-7-1

Cited by 29 publications

(21 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mammalian cells express all five UCP paralogues, which share sequence similarities, but have different tissue distribution. UCP1 is predominantly expressed in BAT and upon hyperglycemia is also expressed in white adipose tissue, skeletal muscle, retinal cells and pancreatic b cells [58, 59, 235,236]. Human UCP2 (SLC25A48) and UCP3 (SLC25A9) have high sequence identity with UCP1: 59 and 57 %, respectively, and *70 % identity with each other [234].…”

Section: The Ucp Familymentioning

confidence: 99%

Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart

2014

View full text Add to dashboard Cite

Despite significant progress in cardiovascular medicine, myocardial ischemia and infarction, progressing eventually to the final end point heart failure (HF), remain the leading cause of morbidity and mortality in the USA. HF is a complex syndrome that results from any structural or functional impairment in ventricular filling or blood ejection. Ultimately, the heart's inability to supply the body's tissues with enough blood may lead to death. Mechanistically, the hallmarks of the failing heart include abnormal energy metabolism, increased production of reactive oxygen species (ROS) and defects in excitation-contraction coupling. HF is a highly dynamic pathological process, and observed alterations in cardiac metabolism and function depend on the disease progression. In the early stages, cardiac remodeling characterized by normal or slightly increased fatty acid (FA) oxidation plays a compensatory, cardioprotective role. However, upon progression of HF, FA oxidation and mitochondrial oxidative activity are decreased, resulting in a significant drop in cardiac ATP levels. In HF, as a compensatory response to decreased oxidative metabolism, glucose uptake and glycolysis are upregulated, but this upregulation is not sufficient to compensate for a drop in ATP production. Elevated mitochondrial ROS generation and ROS-mediated damage, when they overwhelm the cellular antioxidant defense system, induce heart injury and contribute to the progression of HF. Mitochondrial uncoupling proteins (UCPs), which promote proton leak across the inner mitochondrial membrane, have emerged as essential regulators of mitochondrial membrane potential, respiratory activity and ROS generation. Although the physiological role of UCP2 and UCP3, expressed in the heart, has not been clearly established, increasing evidence suggests that these proteins by promoting mild uncoupling could reduce mitochondrial ROS generation and cardiomyocyte apoptosis and ameliorate thereby myocardial function. Further investigation on the alterations in cardiac UCP activity and regulation will advance our understanding of their physiological roles in the healthy and diseased heart and also may facilitate the development of novel and more efficient therapies.

show abstract

Section: The Ucp Familymentioning

confidence: 99%

Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart

2014

View full text Add to dashboard Cite

show abstract

“…Staining with each antibody was further validated using an alkaline phosphatase method (27), which used a biotinylated anti-rabbit secondary antibody as the linking reagent and alkaline phosphataseconjugated streptavidin (BioGenex, San Ramon, CA) for labeling. The Vector red chromogen, obtained as Vector red substrate kit no.…”

Section: Animalsmentioning

confidence: 99%

Localization of the novel angiotensin peptide, angiotensin-(1-12), in heart and kidney of hypertensive and normotensive rats

Jessup¹,

Trask²,

Chappell³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

A low expression of angiotensinogen in the heart has been construed as indicating a circulating uptake mechanism to explain the local effects of angiotensin II on tissues. The recent identification of angiotensin-(1-12) in an array of rat organs suggests this propeptide may be an alternate substrate for local angiotensin production. To test this hypothesis, tissues from 11-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (n ϭ 14) were stained with purified antibodies directed to the COOH terminus of angiotensin-(1-12). Robust angiotensin-(1-12) staining was predominantly found in ventricular myocytes with less staining found in the medial layer of intracoronary arteries and vascular endothelium. In addition, angiotensin-(1-12) immunoreactivity was present in the proximal, distal, and collecting renal tubules within the deep cortical and outer medullary zones in both strains. Preadsorption of the antibody with angiotensin-(1-12) abolished staining in both tissues. Corresponding tissue measurements by radioimmunoassay showed 47% higher levels of angiotensin-(1-12) in the heart of SHR compared with WKY rats (P Ͻ 0.05). In contrast, renal angiotensin-(1-12) levels were 16.5% lower in SHR compared with the WKY rats (P Ͻ 0.05). This study shows for first time the localization of angiotensin-(1-12) in both cardiac myocytes and renal tubular components of WKY and SHR. In addition, we show that increased cardiac angiotensin-(1-12) concentrations in SHR is associated with a small, but statistically significant, reduction in renal angiotensin-(1-12) levels.angiotensinogen; angiotensin I; angiotensin II; hypertension; renin ALTHOUGH NUMEROUS STUDIES have documented the presence of a local renin-angiotensin system (RAS

show abstract

“…Los genes de las proteínas desacoplantes tienen una expresión diferencial: UCP1 se expresa principalmente en el tejido adiposo pardo, la proteína UCP2 es ubicua y la UCP3 se encuentra en mayor cantidad en el tejido adiposo blanco y en el músculo esquelético; sin embargo, recientes investigaciones han mostrado la presencia de UCP1 y UCP3 en células beta pancreáticas (5,9). Su función desacoplante se ha implicado con fenotipos asociados con diabetes mellitus tipo 2 en modelos animales y humanos.…”

unclassified

“…En diversos estudios se han hallado, principalmente, relaciones entre alteraciones en UCP1 y UCP3, con obesidad y metabolismo de lípidos, en UCP2, con fallas en la secreción de insulina, y en UCP2 y UCP3, con protección contra especies reactivas de oxígeno (6,7,10,11). Además, en el último año, UCP1 y UCP3 se han asociado con la secreción de insulina estimulada por glucosa (5,9). Estos hallazgos son apoyados por la asociación de variantes en estos genes con las características fenotípicas mencionadas (11)(12)(13) variantes genéticas que otorgan susceptibilidad a almacenar energía que, en condiciones de escasez, son una ventaja adaptativa y, en condiciones de abundancia, se expresa en forma de enfermedad, en este caso particular como diabetes mellitus tipo 2 (14).…”

unclassified

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

et al. 2009

View full text Add to dashboard Cite

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...

show abstract

The uncoupling protein 1 gene, UCP1, is expressed in mammalian islet cells and associated with acute insulin response to glucose in African American families from the IRAS Family Study

Cited by 29 publications

References 58 publications

Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart

Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart

Localization of the novel angiotensin peptide, angiotensin-(1-12), in heart and kidney of hypertensive and normotensive rats

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

Contact Info

Product

Resources

About