Metabolic signals produced by purine ribonucleosides stimulate proinsulin biosynthesis and insulin secretion.
Inosine, guanosine and adenosine strongly stimulated proinsulin biosynthesis and insulin secretion in isolated mouse pancreatic islets. None of the purine ribonucleosides stimulated insulin secretion in rat islets, although as reported [jain & Logothetopoulos (1977) Endocrinilogy 100, 923-927] inosine and guanosine, but no adenosine, were potent stimulants of proinsulin biosynthesis in this species. The purine bases had no effect in either species. D-Ribose, which enhanced proinsulin biosynthesis at 0.3 and 0.6 mM but not at 5mM in rat pancreatic islets [jain & Logothetopoulos (1977) Endocrinology 100, 923-927], produced no secretory signals in rat islets and was without any effect on proinsulin biosynthesis and insulin secretion in mouse islets. The rates of oxidation of 14C-labelled purine ribonucleosides and D-ribose in islets of the two species correlated well with their effectiveness as inducers of insulin secretion and proinsulin biosynthesis. Specific inhibitors of purine ribonucleoside phosphorylase, adenosine deaminiase and of purine ribonucleoside transport suppressed the stimulatory effects of nucleosides in pancreatic islets without altering the effect of D-glucose. The same inhibitors also markedly diminished the oxidation rats of the labelled purine ribonucleosides. The experiments clearly indicate that porinsulin biosynthesis and insulin secretion are modulated through metabolic signals and not through interactions of intact substrate molecules with cell receptors.
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008356:Mannoheptulose / Q000494:pharmacology; D051379:Mice; D011384:Proinsulin / Q000096:biosynthesis*; D011684:Purine Nucleosides / Q000378:metabolism*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D012263:Ribonucleosides / Q000494:pharmacology; D012266:Ribose / Q000494:pharmacology; D013872:Thionucleosides / Q000494:pharmacology
D001381:Azepines; D007328:Insulin; D011684:Purine Nucleosides; D011687:Purines; D012263:Ribonucleosides; D013872:Thionucleosides; D006151:Guanosine; D002245:Carbon Dioxide; D008356:Mannoheptulose; D012266:Ribose; D011384:Proinsulin; D005947:Glucose