Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Idoso , Antineoplásicos/uso terapêutico , Meios de Contraste , Feminino , Humanos , Imageamento Tridimensional , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Intensificação de Imagem Radiográfica , Resultado do TratamentoAssuntos
Ablação por Cateter , Neoplasias Colorretais/patologia , Meios de Contraste , Tomografia Computadorizada Quadridimensional/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Intensificação de Imagem Radiográfica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/cirurgia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoAssuntos
Neoplasias Abdominais/tratamento farmacológico , Neoplasias Colorretais/patologia , Meios de Contraste , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Intensificação de Imagem Radiográfica/métodos , Neoplasias Abdominais/diagnóstico por imagem , Idoso , Biomarcadores , Feminino , Tomografia Computadorizada Quadridimensional/métodos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Critérios de Avaliação de Resposta em Tumores Sólidos , Resultado do Tratamento , Ácidos Tri-IodobenzoicosRESUMO
Context: Lipoprotein lipase (LPL) activity is considered the rate-limiting step of very-low-density-lipoprotein triglycerides (VLDL-TG) tissue storage, and has been suggested to relate to the development of obesity as well as insulin resistance and type 2 diabetes. Objective: The objective of the study was to assess the relationship between the quantitative storage of VLDL-TG fatty acids and LPL activity and other storage factors in muscle and adipose tissue. In addition, we examine whether such relations were influenced by type 2 diabetes. Design: We recruited 23 men (12 with type 2 diabetes, 11 nondiabetic) matched for age and body mass index. Postabsorptive VLDL-TG muscle and subcutaneous adipose tissue (abdominal and leg) quantitative storage was measured using tissue biopsies in combination with a primed-constant infusion of ex vivo triolein labeled [1-14C]VLDL-TG and a bolus infusion of ex vivo triolein labeled [9,10-3H]VLDL-TG. Biopsies were analyzed for LPL activity and cellular storage factors. Results: VLDL-TG storage rate was significantly greater in men with type 2 diabetes compared with nondiabetic men in muscle tissue (P = 0.02). We found no significant relationship between VLDL-TG storage rate and LPL activity or other storage factors in muscle or adipose tissue. However, LPL activity correlated with fractional VLDL-TG storage in abdominal fat (P = 0.04). Conclusions: Men with type 2 diabetes have increased VLDL-TG storage in muscle tissue, potentially contributing to increased intramyocellular triglyceride and ectopic lipid deposition. Neither muscle nor adipose tissue storage rates were related to LPL activity. This argues against LPL as a rate-limiting step in the postabsorptive quantitative storage of VLDL-TG.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Lipase Lipoproteica/metabolismo , Lipoproteínas VLDL/metabolismo , Músculo Esquelético/metabolismo , Gordura Subcutânea/metabolismo , Triglicerídeos/metabolismo , Absorciometria de Fóton , Adulto , Idoso , Composição Corporal , Antígenos CD36/metabolismo , Radioisótopos de Carbono , Estudos de Casos e Controles , Coenzima A Ligases/metabolismo , Diacilglicerol O-Aciltransferase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , TrítioRESUMO
OBJECTIVE: Increased very-low-density lipoprotein triglycerides (VLDL-TG) concentration is a central feature of diabetic dyslipidemia. The objective was to compare basal and insulin mediated VLDL-TG kinetics, oxidation, and adipose tissue storage in type 2 diabetic and healthy (nondiabetic) men. RESEARCH DESIGN AND METHODS: Eleven type 2 diabetic and 11 healthy men, matched for BMI and age, were included. Ex vivo-labeled VLDL-TG tracers, blood and breath samples, fat biopsies, indirect calorimetry, and body composition measures were applied to determine VLDL-TG kinetics, VLDL-TG fatty acids (FA) oxidation, and storage in regional adipose tissue before and during a hyperinsulinemic euglycaemic clamp. RESULTS: VLDL-TG secretion was significantly greater in diabetic compared with healthy men (basal: 86.9 [31.0] vs. 61.9 [30.0] µmol/min, P = 0.03; clamp: 60.0 [26.2] vs. 34.2 [17.9] µmol · min⻹, P = 0.01). The insulin mediated suppression of VLDL-TG secretion was significant in both groups. VLDL-TG clearance was lower in diabetic men (basal: 84.6 [32.7] vs. 115.4 [44.3] ml · min⻹, P = 0.08; clamp: 76.3 [30.6] vs. 119.0 [50.2] ml · min⻹, P = 0.03). During hyperinsulinemia fractional VLDL-TG FA oxidation was comparable, but in percentage of energy expenditure (EE), significantly higher in diabetic men. Basal VLDL-TG storage was similar, but significantly greater in abdominal compared with leg fat. CONCLUSIONS: Increased VLDL-TG in type 2 diabetic men is caused by greater VLDL-TG secretion and less so by lower VLDL-TG clearance. The ability of hyperinsulinemia to suppress VLDL-TG secretion appears preserved. During hyperinsulinemia VLDL-TG FA oxidation is significantly increased in proportion of EE in type 2 diabetic men. Greater basal abdominal VLDL-TG storage may help explain the accumulation of upper-body fat in insulin-resistant individuals.
