STRUCTURAL SPECIFICITY OF NUCLEOTIDES FOR INSULIN SECRETORY ACTION FROM THE ISOLATED PERFUSED RAT PANCREAS

The study concerned the effects of various nucleotides on the insulin secretion from the isolated perfused at pancreas. ATP, the first nucleotide studied, increased the insulin release induced by glucose 1.5 g/l. There was a first immediate peak followed by a second significant and durable increase. The log dose-response curve was linear for concentrations ranging from 0.825 μM to 330 μM. The effects of natural adenine derivatives (ATP, ADP, 5′AMP, cAMP and adenosine) were compared. ATP was the most active compound; ADP had nearly the same activity as ATP (relative potency ATP/ADP = 3.2); 5′AMP, cAMP and adenosine displayed a very weak activity (about 100 fold less active). Adenylimido-diphosphate (AMP-PNP), a non-phosphorylating structural analogue of ATP, clearly stimulated insulin secretion and its effect was concentration-related. It was about 10 folds less active than ATP. The comparison of triphosphorylated derivatives from various nucleosides (ATP, GTP, ITP) or pyrimidine nucleosides (CTP and UTP) showed that only the purine derivatives had a strong insuling secretory effect with, in order of decreasing activity: ATP > GTP > ITP. These results show that certain structural features (purine basis and di- or triphosphate group) are essential to elicit an insuling secretory effect. © 1979.