Differential inhibitory action of cationic amino acids on protein synthesis in pancreatic rat islets.
The effect of cationic amino acids, i.e. L-arginine and L-lysine, on protein synthesis in isolated rat islets of Langerhans has been investigated. Except for prosomatostatin, the formation of islet proteins is strongly depressed by these amino acids. This effect can be demonstrated within a few minutes and is rapidly reversible. For proglucagon, efficient concentrations of arginine are in the range of 1 to 10 mmol/l. The sensitivity of proinsulin formation to arginine is glucose-dependent: at 2.5 mmol/l, inhibitory concentrations of arginine are 10-fold lower than in the case of proglucagon. High glucose (20 mmol/l) almost completely protects proinsulin synthesis from this inhibition. The proteolytic conversion steps in hormonal precursor processing are not influenced by cationic amino acids as studied in intact islets and in a cell-free translational system. It is concluded that arginine and lysine inhibit protein synthesis in islet cells at the translational level. The release of these amino acids by prohormone conversion may exert a feed-back control on proinsulin formation that is modulated by glucose.
D000596:Amino Acids / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000032:analysis / Q000494:pharmacology; D002412:Cations / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects*; D008239:Lysine / Q000494:pharmacology; D009952:Ornithine / Q000494:pharmacology; D011384:Proinsulin / Q000096:biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000596:Amino Acids; D002412:Cations; D011500:Protein Synthesis Inhibitors; D011384:Proinsulin; D001120:Arginine; D009952:Ornithine; D005947:Glucose; D008239:Lysine