Cardiac glucose and fatty acid oxidation in the streptozotocin-induced diabetic spontaneously hypertensive rat.
Hypertension intensifies the cardiac dysfunction of diabetes. We investigated the possible role of altered exogenous fuel oxidation in this phenomenon. Diabetes was induced by streptozotocin in spontaneously hypertensive rats and normotensive Sprague-Dawley rats. Two weeks later, mechanical performance and the oxidation of glucose and palmitate were quantified in working hearts ex vivo at intermediate and high workloads. The results showed that the nondiabetic spontaneously hypertensive rat hearts, compared with those of the normotensive controls, oxidized glucose at a higher rate but oxidized palmitate at a much lower rate, as reported previously. The effects of diabetes in the hypertensive rats, compared with its effects in the normotensive strain, were characterized by (1) a more pronounced decrease in heart performance, (2) either a similar or a less marked reduction in the rate of glucose oxidation, depending on the workload, and (3) a relatively greater increase in palmitate oxidation, particularly at the higher workload. These findings suggest that the exaggerated stimulation of fatty acid oxidation by diabetes in the hypertrophic left ventricle may be a more important contributor to the premature mechanical dysfunction than the inhibition of glucose oxidation. Possible mechanisms include antagonism of energetically favorable shifts in fuel oxidation or inhibition of accelerated membrane lipid biosynthesis in left ventricular hypertrophy.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Rhode Island, Kingston 02881.
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Christe
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Rodgers
D000818:Animals; D002331:Carnitine / Q000378:metabolism; D003065:Coenzyme A / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D005227:Fatty Acids; D010710:Phosphates; D005947:Glucose; D002331:Carnitine; D003065:Coenzyme A