Nucleoside-stimulated insulin production by isolated mouse pancreatic islets.

Purine ribonucleosides were found to be as potent stimulators of proinsulin biosynthesis as glucose, adenosine being effective at very low concentrations (0.1 mM). Some pyrimidine nucleosides together with 2-deoxyribonucleoside (thymidine) were also potent stimulants. The single components of nucleosides (pentoses and bases) had no, or only slight, stimulatory effects. Nucleosides added to a low-glucose culture medium were found to replace glucose as a long-term stimulant of the insulin biosynthesis of islets in culture. Adenosine-stimulated insulin secretion from perifused islets was biphasic, although kinetic differences were observed as compared with glucose stimulation. The rate of oxidation of [U-14C]-adenosine was dose dependent, whereas no production of 14CO2 was obtained during incubation of islets in [8-14C]-adenosine. Oxidation of 14C-labelled glucose was depressed by addition of adenosine. The results add further support to the view that nucleoside-stimulated insulin secretion and biosynthesis are modulated through metabolic signals.