Insulin Action in Isolated Rat Thymocytes: II. INDEPENDENCE OF INSULIN AND CYCLIC ADENOSINE MONOPHOSPHATE

Abstract

Abstract Dibutyryl cyclic adenosine 3',5'-monophosphate(dibutyryl cyclic AMP), cyclic adenosine 3',5'-monophosphate (cyclic AMP), and prostaglandin E1 (PGE1) stimulated α-aminoisobutyric acid (AIB) influx in thymocytes from suckling rats. Dibutyryl cyclic AMP increased influx at concentrations as low as 30 µm; a maximal effect was seen at 1 mm. Cyclic AMP had 1% of the activity of its dibutyryl derivative. PGE1 increased AIB influx at concentrations as low as 30 nm. Dibutyryl cyclic AMP increased AIB influx by increasing the maximal influx capacity (Jmax) without affecting the Km. This is in contrast to the effect of insulin which, in addition to raising the Jmax, also lowers the Km. When insulin was added with either PGE1 or dibutyryl cyclic AMP, the effects were additive. PGE1 elevated thymocyte cyclic AMP levels, whereas insulin neither lowered basal cyclic AMP levels nor blocked the rise in cyclic AMP produced by PGE1. We concluded that (a) insulin increased AIB influx by a mechanism not involving changes in cyclic AMP levels, and (b) cyclic AMP and prostaglandin E1 increased AIB influx by a different mechanism than insulin.