The regulation of the biosynthesis of the insulin-secretory-granule matrix proteins insulin II, chromogranin A and carboxypeptidase H was studied in isolated rat islets of Langerhans. Islets were labelled with [35S]-methionine, and incorporation into total protein was determined by trichloroacetic acid precipitation and that into specific proteins by immunoprecipitation followed by polyacrylamide-gel electrophoresis and fluorography. Islets incubated in the presence of 16.7 mM-glucose incorporated 3 times as much [35S]-methionine into total protein as did islets incubated with 2.8 mM-glucose. The same conditions produced more than a 20-fold increase in incorporation into both proinsulin and chromogranin A, with no observable effect on carboxypeptidase H. The concentration-dependencies of the glucose-stimulated synthesis of chromogranin A and proinsulin were parallel, and in both cases the response to 16.7 mM-glucose was typified by an initial lag of 20 min, followed by a rapid activation to a new steady state over the ensuing 40 min. Synthesis of total protein, although activated to a lesser extent, responded with similar kinetics. Extracellular Ca2+ depletion did not affect the basal or glucose-stimulated biosynthesis of any of the proteins under investigation. Mannoheptulose (20 mM) abolished glucose-stimulated synthesis of insulin, chromogranin A and total protein, but had no effect on the synthesis of carboxypeptidase H. It is concluded that the biosynthesis of insulin and chromogranin A is regulated principally at the translational level by the same intracellular signal generated from the metabolism of glucose. Such regulation is not common to all insulin-secretory-granule proteins, since the synthesis of carboxypeptidase H was unaffected by the same stimulus.
Regulation of the biosynthesis of insulin-secretory-granule proteins. Co-ordinate translational control is exerted on some, but not all, granule matrix constituents
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P C Guest, C J Rhodes, J C Hutton; Regulation of the biosynthesis of insulin-secretory-granule proteins. Co-ordinate translational control is exerted on some, but not all, granule matrix constituents. Biochem J 15 January 1989; 257 (2): 431–437. doi: https://doi.org/10.1042/bj2570431
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