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.