Metalloendoprotease inhibitors which block the differentiation of L6 myoblasts inhibit insulin degradation by the endogenous insulin-degrading enzyme.
The cultured myoblasts of the rat skeletal muscle cell line L6 proliferate till confluency and then fuse to form myotubes and express a number of muscle-specific proteins. We had shown that this differentiation process is blocked by specific metalloendoprotease inhibitors. We now demonstrate that metabolizing L6 myoblasts and their cell extracts degrade insulin to acid-soluble fragments by a non-lysosomal pathway. About 90% of the insulin-degrading activity residues in the cytoplasm and is due to a 110-kDa enzyme known as the insulin-degrading enzyme. The same metalloendoprotease inhibitors that block the differentiation of L6 myoblasts also inhibit insulin degradation by the metabolizing L6 cells, their cell extracts, and the insulin-degrading enzyme immunoprecipitated from the cytosolic extracts by a monoclonal antibody. These results suggest that the insulin-degrading enzyme is the metalloendoprotease whose activity is required for the initiation of the morphological and biochemical differentiation of L6 myoblasts.
Kayalar
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Molecular Biology Institute, University of California, Los Angeles 90024-1570.
Wong
W T
WT
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002999:Clone Cells; D007328:Insulin / Q000378:metabolism*; D007339:Insulysin / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010447:Peptide Hydrolases; D011480:Protease Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007328:Insulin; D011480:Protease Inhibitors; D010447:Peptide Hydrolases; D008666:Metalloendopeptidases; D007339:Insulysin