Influence of diadenosine tetraphosphate (Ap4A) on lipid metabolism

Diadenosine polyphosphates (ApxA) are physiologically released and may be partly involved in the pathogenesis of diabetes mellitus. Ap4A (diadenosine tetraphosphate) leads to an increase in blood glucose while it decreases insulin levels in plasma. A possible link between ApxA and diabetes mellitus‐associated diseases such as insulin resistance and hyperlipidemia (plasma free fatty acids, cholesterol and its biosynthesis, triacylglycerols) has not been investigated yet. Parameters such as free fatty acid and cholesterol content in blood were determined enzymically. The biosynthesis of cholesterol and triacylglycerols was determined in HepG2 cells using the radioactive precursor [14C]‐acetate and by using gas chromatography. Plasma free fatty acids were significantly decreased 5 and 10 min after an Ap4A bolus (0.75 mg kg−1 b.w.) given to rats. Plasma cholesterol was reduced 5 and 60 min after Ap4A administration. LPDS (lipoprotein‐deficient serum)‐stimulated cholesterol biosynthesis in HepG2 cells was significantly reduced after 1 h incubation with Ap4A. Triacylglycerol (TAG) biosynthesis in HepG2 cells was not significantly influenced by Ap4A; there was just a tendency for a concentration‐dependent decrease in TAG levels. In conclusion Ap4A as a diabetogenetic compound is not likely to be responsible for the development of insulin resistance or of hyperlipidemia. Parameters such as free fatty acids, cholesterol and triacylglycerols are not elevated by Ap4A, but are even decreased. Ap4A seems to be involved in the development of diabetes mellitus by increasing blood glucose and decreasing plasma insulin as shown earlier, but not in diabetes mellitus‐associated diseases such as insulin resistance or hyperlipidemia. Copyright © 2004 John Wiley & Sons, Ltd.