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Exp Physiol ; 96(8): 765-77, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21666035

RESUMEN

Given the clinical prevalence of type 2 diabetes and obesity and their association with high mortality linked to cardiovascular disease, the aim of the study was to investigate the effects of feeding type 2 diabetic Goto-Kakizaki (GK) rats either high- or low-fat diets on cardiomyocyte structure and function. The GK rats were fed either a high-fat diet (HFD) or a low-fat diet (LFD) from the age of 2 months for a period of 7 months. The GK-HFD rats gained more weight, ate less food and drank less water compared with GK-LFD rats. At 7 months, non-fasting blood glucose was higher in GK-LFD (334 ± 35 mg dl(-1)) compared with GK-HFD rats (235 ± 26 mg dl(-1)). Feeding GK rats with a HFD had no significant effect on glucose clearance following a glucose challenge. Time-to-peak (t(peak)) shortening was reduced in myocytes from GK-HFD (131.8 ± 2.1 ms) compared with GK-LFD rats (144.5 ± 3.0 ms), and time-to-half (t(1/2)) relaxation of shortening was also reduced in myocytes from GK-HFD (71.7 ± 6.9 ms) compared with GK-LFD rats (86.1 ± 3.6 ms). The HFD had no significant effect on the amplitude of shortening. The HFD had no significant effect on t(peak), t(1/2) decay, amplitude of the Ca(2+) transient, myofilament sensitivity to Ca(2+), sarcoplasmic reticulum Ca(2+) content, fractional release of Ca(2+) and the rate of Ca(2+) uptake. Structurally, ventricular myocytes from GK-HFD rats showed extensive mitochondrial lesions, including swelling, loss of cristae, and loss of inner and outer membranes, resulting in gross vacuolarization and deformation of ventricular mitochondria with a subsequent reduction in mitochondrial density. Expression of genes encoding various L-type Ca(2+) channel proteins (Cacnb2) and cardiac muscle proteins (Myl2 and Atp2a1) were downregulated in GK-HFD compared with GK-LFD rats. Structural lesions and changed expression of genes encoding various cardiac muscle proteins might partly underlie the altered time course of myocyte shortening and relaxation in myocytes from GK-HFD compared with GK-LFD rats.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Proteínas Musculares/biosíntesis , Proteínas Musculares/genética , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Disfunción Ventricular/genética , Disfunción Ventricular/metabolismo , Animales , Glucemia/metabolismo , Calcio/metabolismo , Canales de Calcio Tipo L/genética , Canales de Calcio Tipo L/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Dieta con Restricción de Grasas/métodos , Dieta Alta en Grasa/métodos , Regulación hacia Abajo , Ayuno/metabolismo , Expresión Génica , Masculino , Mitocondrias/metabolismo , Mitocondrias/patología , Miofibrillas/metabolismo , Ratas , Retículo Sarcoplasmático/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Disfunción Ventricular/patología
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