The influence of thioctic acid on metabolism and function of the diabetic heart.
Streptozotocin-diabetes as a model for insulin-deficient Type 1 diabetes leads to cardiomyopathy, characterized by a 50% reduced glucose uptake (P < 0.001) and increased lactate and pyruvate levels (P < 0.001), i.e. a reduced glucose utilization by the heart. As thioctic acid (TA) has favourable effects on glucose metabolism, the influence of this drug at two different doses (0.1 mg/ml and 0.5 mg/ml, added to the perfusion medium) was investigated in the heart after 2 weeks of diabetes, using the working rat heart model at physiological workload about 45 min. TA at high doses led to a normalization of glucose uptake (P < 0.001) and glucose utilization, and consequently to a normalization of oxygen uptake (P < 0.001), myocardial ATP levels (P < 0.001) as well as cardiac output (P < 0.05). Whereas a low dose of TA resulted in a normalization of lactate and pyruvate production (P < 0.001), neither a normalization of glucose utilization nor of cardiac output was achieved by this low dosage. Additionally, TA improved at both doses utilization of endogenous glycogen in the diabetic heart (P < 0.001), the latter here already delivering 45% of the utilized glucose. TA acts especially by increasing glucose uptake, glycogen breakdown and glucose oxidation. Thus, metabolic and hemodynamic sequelae of insulin-deficiency in the heart can be corrected by TA. Due to its anti-diabetic effects on cardiac metabolism, TA could be considered an adjuvant therapy in diabetic cardiomyopathy.
Strödter
D
D
Medical Clinic III, University of Giessen, Germany.
Lehmann
E
E
Lehmann
U
U
Tritschler
H J
HJ
Bretzel
R G
RG
Federlin
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D008063:Thioctic Acid / Q000008:administration & dosage*
D008063:Thioctic Acid; D000255:Adenosine Triphosphate; D005947:Glucose