Stimulation of Proinsulin Biosynthesis by Purine-Ribonucleosides and D-Ribose

Abstract

Inosine and guanosine were potent stimuli of proinsulin biosynthesis ([3H]leucine incorporation) in isolated pancreatic islets of the rat. The effect was nearly abolished by formycin B, an inhibitor of purine nucleoside phosphorylase, but not by D-mannoheptulose. The corresponding bases had no effect on the rate of proinsulin biosynthesis. D-ribose enhance proinsulin biosynthesis at low concentrations )0.3-0.6mM) but concentrations above 5 mM were ineffective. The effect of all three compounds was highly specific for proinsulin biosynthesis, since incorporation of [3H]leucine into other islet proteins was not significantly stimulated. The data strongly indicate that metabolic signals regulate modulation of proinsulin biosynthesis in the beta cells.

The effect of sugars on (pro)insulin biosynthesis

“…The inability of L-glucose, fructose, galactose and ribose to stimulate (pro)insulin biosynthesis has been previously reported (Lin & Haist, 1969;Pipeleers etal., 1973a;Ashcroft etal., 1976). The stimulation of (pro)insulin biosynthesis by low concentrations of ribose that do not stimulate insulin release (Jain & Logothetopoulos, 1977) could not be confirmed in the present study. One apparent exception is N-acetylglucosamine, which was a strong stimulator of (pro)insulin biosynthesis in the absence of glucose, but whose stimulatory effect on insulin release has been reported to require the presence of a substimulatory concentration of glucose .…”

A species difference in nucleoside phosphorylase activity and inosine-stimulated insulin secretion in isolated islets of Langerhans

“…It is unclear whether the effects of nucleosides on insulin biosynthesis and release (Jain & Logothetopoulos, 1977;Ismail et al, 1977) are in any way related to the stimulatory effect of glucose on islets. The observed difference, however, in nucleoside phosphorylase activity between rabbit and rat islets suggests that, for inosine, the primary stimulus for insulin release is a metabolic product of the nucleoside.…”

“…Inosine has been shown to stimulate insulin secretion from isolated mouse islets of Langerhans (Capito & Hedeskov, 1976) and insulin biosynthesis in isolated rat islets of Langerhans (Jain & Logothetopoulos, 1977). Capito & Hedeskov (1976) demonstrated the presence, in homogenates of mouse islets of Langerhans, of a nucleoside phosphorylase capable of splitting inosine to hypoxanthine and ribose 1-phosphate, and concluded that an intermediate of inosine metabolism may trigger insulin release.…”

Opposite effects of starvation on oxidation of [14C]adenosine and adenosine-induced insulin release by isolated mouse pancreatic islets

“…Further support for the substrate-site hypothesis emerged from the observations that various purine ribonucleosides were potent primary stimulators of insulin secretion (Capito & Hedeskov, 1976) and insulin biosynthesis (Jain & Logothetopoulos, 1977, 1978Andersson & Hellerstrom, 1977;Ashcroft & Hedeskov, 1978). The stimulatory effect is presumably due to the splitting of ribonucleosides into the purine base and ribose 1-phosphate, the ribose moiety being then further metabolized via the pentose phosphate cycle with the formation of glycolytic intermediates.…”