Diadenosine tetraphosphate (Ap4A) induces a diabetogenic situation: its impact on blood glucose, plasma insulin, gluconeogenesis, glucose uptake and GLUT-4 transporters.

Diadenosine polyphosphates such as Ap4A are physiologically released compounds for which both receptors as well as a role as second messengers for influencing insulin release have been shown. So far little is known about their pathophysiological impact on diabetes with respect to blood glucose and plasma insulin, glucose production via gluconeogenesis, glucose uptake and GLUT-4 expression. Rats given an intravenous bolus of Ap4A (0.75 mg/kg) developed a rapid and dramatic increase in blood glucose. Plasma insulin was only transiently increased (for 4 min), but did not follow the normally stimulatory effect of the elevated blood glucose. A bolus of 25 microg Ap4A quickly increased glucose release from perfused rat liver. Glucose uptake was reduced in 3T3 adipocytes. Reduced amounts of translocated GLUT-4 were found in 3T3 cell membranes incubated with 10 microM Ap4A. Thus, Ap4A itself induces a diabetic situation which is likely to be mediated by an increase in gluconeogenesis and/or an insulin resistance caused by a decrease in GLUT-4 and an attenuation of glucose uptake.