Specificity of Nucleotide-Induced Insulin Secretion

The structural specificity for nucleotide-stimulated insulin secretion was studied n i an in vitro golden hamster pancreas system. Cyclic 3′,5′-adenosine monophosphate (cAMP) was the most effective cyclic nucleotide in stimulating insulin secretion. The cyclic nucleotides of uridine, cytidine, inosine and guanosine did not stimulate significant insulin secretion. In the nucleoside triphosphate series, adenosine triphos-phate and guanosine triphosphate are equally effective in stimulating insulin secretion. Inosine triphosphate is a weaker stimulator of insulin secretion than adenosine triphosphate; uridine and cytidine triphosphate do not significantly stimulate insulin secretion. The structural subunits of adenosine triphosphate stimulate insulin secretion with the following decreasing order of effectiveness: adenosine > adenosine diphosphate. Adenosine monophosphate does not stimulate significant insulin secretion. Adenosine may be the most effective of the subunits because it enters intact cells more readily than the nucleotides. Phospho-creatine, uridine and adenine do not stimulate insulin secretion. We conclude that there is con siderable structural specificity for nucleotide-induced insulin secretion. (Endocrinology94: 388, 1974)