MYOCARDIAL-METABOLISM OF PANTOTHENIC-ACID IN CHRONICALLY DIABETIC RATS

Transport and metabolism of [3H]pantothenic acid ([3H]Pa) was investigated in hearts from control and streptozotocin-induced diabetic rats. In isolated perfused hearts from control animals, the transport of [3H]Pa was linear over 3 h of perfusion when 11 mm glucose was the only exogenous substrate. The in vitro transport of [3H]Pa by hearts from 48-h diabetic rats was reduced by 65% compared to controls and was linear over 2 h of perfusion with no further accumulation of Pa during the third hour. The defect in transport observed in vitro could be corrected by in vivo treatment with 4 U Lente insulin/day for 2 days. In vitro addition of insulin in the presence of 11 mm glucose or 11 mm glucose plus 1.2 mm palmitate had no effect on [3H]Pa transport in hearts from 48-h diabetic rats during 3 h of perfusion. Accumulation of [3H]Pa was not inhibited by inclusion of 0.7 mm amino acids, 1 mm carnitine, 50 μm mersalic acid or 1 mm panthenol, pantoyllactone or pantoyltaurine. Uptake was inhibited by 1 mm nonanoic, octanoic or heptanoic acid, 0.1 mm biotin or 0.25 mm probenecid, suggesting a requirement for the terminal carboxyl group for transport. Transport of pantothenic acid was reduced in hearts from diabetic rats within 24 h of injection of streptozotocin. In vitro accumulation of [3H]Pa decreased to 10% of control 1 week after streptozotocin injection and then remained at 30% of the control value over 10 weeks. The in vivo myocardial pantothenic acid content followed a similar course with levels decreasing to 40% of control value 3 weeks after induction of diabetes and remaining at that level over 10 weeks. Total CoA levels in hearts from diabetic rats were increased within 24 h of streptozotocin injection and remained elevated over 10 weeks of diabetes. The increase was primarily the result of higher acyl CoA. Thus, although decreased transport resulted in decreased myocardial Pa levels during chronic diabetes, intracellular Pa (67 μm) was above the Km of Pa kinase (18 μm) and did not become rate limiting in CoA synthesis. © 1990.