Analysis of proinsulin conversion activated by prior glucose: evidence that glucose stimulates synthesis of the conversion enzyme.
We examined the mechanism by which prior glucose exposure accelerates conversion of proinsulin to insulin in pancreatic islets. Using actinomycin A, introduced at different times after a 3H-leucine pulse to block the intracellular transport of proinsulin, transport was found to be slightly accelerated after prolonged glucose. However, computer simulation of pulse-chase experiments showed that activation of conversion is mostly due to increased converting activity. Measurement of islet procathepsin B by immunoprecipitation indicated synthesis of this enzyme was stimulated about two fold after glucose. Pre-exposure with tunicamycin inhibited the acceleration of conversion, suggesting that the converting system requires glycosylation.
Nagamatsu
S
S
Metabolic Research Unit, University of California, San Francisco 94143.
Grodsky
G M
GM
D000968:Antimycin A / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003198:Computer Simulation; D003594:Cytoplasmic Granules / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000378:metabolism*; D011384:Proinsulin / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology
D007328:Insulin; D014415:Tunicamycin; D000968:Antimycin A; D011384:Proinsulin; D005947:Glucose