The effect of diabetes on mevalonate metabolism in the rat

Previous studies have demonstrated a major difference in mevalonate metabolism by male and female rats by both the shunt and sterol pathways. This important sex difference was shown to be related to the presence of oestrogens and/or progesterone. In the present study we have investigated the effects of streptozotocin-induced diabetes on mevalonate metabolism. Firstly, insulin deficiency decreased the ability of the rats to oxidize mevalonate to carbon dioxide by the shunt pathway both in vivo and in vitro. This decrease was reversed by insulin treatment both in the intact animals as well as in tissue slices. Secondly, diabetes caused a marked increase in hepatic sterologenesis in the intact animal. This is the first demonstration that insulin plays significant regulatory role in both the shunt and sterol pathways of mevalonate metabolism.