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1.
J Diabetes Investig ; 10(1): 94-103, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29862667

RESUMO

AIMS/INTRODUCTION: There is controversy as to whether hyperuricemia is an independent risk factor for cardiometabolic diseases. The serum level of uric acid is affected by a wide variety of factors involved in its production and excretion. In contrast, evidence has accumulated that locally- and systemically-activated xanthine oxidase (XO), a rate-limiting enzyme for production of uric acid, is linked to metabolic derangement in humans and rodents. We therefore explored the clinical implication of plasma XO activity in patients with type 2 diabetes mellitus and metabolic syndrome (MetS). MATERIALS AND METHODS: We enrolled 60 patients with type 2 diabetes mellitus and MetS. MetS was defined according to the 2005 International Diabetes Federation guidelines. Plasma XO activity was measured by highly-sensitive fluorometric assay measuring the conversion of pterin to isoxanthopterin, and explored associations between the value of plasma XO activity and metabolic parameters. RESULTS: The value of plasma XO activity was correlated with indices of insulin resistance and the level of circulating liver transaminases. In contrast, the level of serum uric acid was not correlated with indices of insulin resistance. The value of plasma XO activity was not correlated with the serum uric acid level. CONCLUSIONS: Plasma XO activity correlates with indices of insulin resistance and liver dysfunction in Japanese patients with type 2 diabetes mellitus and MetS. Through assessing the plasma XO activity, patients showing normal levels of serum uric acid with higher activity of XO can be screened, thereby possibly providing a clue to uncovering metabolic risks in type 2 diabetes mellitus and MetS patients.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Resistência à Insulina , Hepatopatias/sangue , Síndrome Metabólica/sangue , Xantina Oxidase/sangue , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Hepatopatias/complicações , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco , Adulto Jovem
2.
Intern Med ; 52(14): 1561-71, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23857087

RESUMO

Objective In addition to excess visceral fat, lipid deposition in the liver and skeletal muscle has been implicated in the pathophysiology of type 2 diabetes and metabolic syndrome. This study was designed to explore the relationship between hepatic and muscular lipid deposition and visceral fat accumulation in 105 middle-aged men with metabolic syndrome. Methods Abdominal computed tomography (CT) was used to simultaneously evaluate the visceral fat area (VFA) and CT Hounsfield unit (HU) values of three different portions of skeletal muscle and the liver. Results A significant inverse correlation was observed between the VFA and the CT HU values of the iliopsoas muscle, back muscle, rectus abdominis muscle and liver. Three types of interventions, i.e., lifestyle modification and treatment with antidiabetic drugs, such as Pioglitazone or Miglitol, caused significant decreases in visceral fat accumulation. The extent of lipid deposition in the liver was strongly correlated with the levels of glucose-lipid metabolic markers, which decreased significantly following Pioglitazone treatment. On the other hand, the amount of lipid deposition in the three skeletal muscles and the liver did not decrease after Miglitol treatment. Conclusion Visceral fat accumulation is accompanied by excess lipid deposition in skeletal muscle and the liver in patients with metabolic syndrome. The CT-based simultaneous, concise evaluations of ectopic lipid deposition and visceral fat mass used in the present study may provide unique information for assessing cardiometabolic risks and the therapeutic impact in patients with diabetes-obesity syndrome.


Assuntos
Fígado Gorduroso/metabolismo , Hipoglicemiantes/uso terapêutico , Gordura Intra-Abdominal/metabolismo , Metabolismo dos Lipídeos/fisiologia , Síndrome Metabólica/terapia , Comportamento de Redução do Risco , Adulto , Idoso , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/terapia , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/fisiopatologia , Masculino , Síndrome Metabólica/diagnóstico por imagem , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Tomografia Computadorizada por Raios X
3.
Diabetes ; 61(12): 3084-93, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22826028

RESUMO

Brown rice is known to improve glucose intolerance and prevent the onset of diabetes. However, the underlying mechanisms remain obscure. In the current study, we investigated the effect of brown rice and its major component, γ-oryzanol (Orz), on feeding behavior and fuel homeostasis in mice. When mice were allowed free access to a brown rice-containing chow diet (CD) and a high-fat diet (HFD), they significantly preferred CD to HFD. To reduce hypothalamic endoplasmic reticulum (ER) stress on an HFD, mice were administered with 4-phenylbutyric acid, a chemical chaperone, which caused them to prefer the CD. Notably, oral administration of Orz, a mixture of major bioactive components in brown rice, also improved glucose intolerance and attenuated hypothalamic ER stress in mice fed the HFD. In murine primary neuronal cells, Orz attenuated the tunicamycin-induced ER stress. In luciferase reporter assays in human embryonic kidney 293 cells, Orz suppressed the activation of ER stress-responsive cis-acting elements and unfolded protein response element, suggesting that Orz acts as a chemical chaperone in viable cells. Collectively, the current study is the first demonstration that brown rice and Orz improve glucose metabolism, reduce hypothalamic ER stress, and, consequently, attenuate the preference for dietary fat in mice fed an HFD.


Assuntos
Dieta Hiperlipídica , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Oryza/metabolismo , Fenilpropionatos/farmacologia , Animais , Western Blotting , Peso Corporal/efeitos dos fármacos , Células Cultivadas , Ingestão de Alimentos/efeitos dos fármacos , Teste de Tolerância a Glucose , Camundongos , Camundongos Endogâmicos C57BL , Fenilbutiratos/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Triglicerídeos/metabolismo
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