title: The calcium dependence of insulin degradation by rat skeletal muscle.
abstract: The effect of calcium on insulin degradation by intact or homogenized skeletal muscle, by skeletal muscle cytosol, and by partially purified skeletal muscle insulin-degrading protease activity was examined. After a 15-min lag phase, intact soleus muscles degraded [125I]insulin to trichloroacetic acid-soluble products in a time-dependent fashion. Degradation was accelerated by the addition of calcium (greater than or equal to 1 mM), such that maximal stimulation (2-fold) was obtained with 10 or 25 mM calcium. Calcium stimulated insulin degradation by skeletal muscle homogenate and by cytosol in a nearly identical manner. Furthermore, after inactivation of the purified skeletal muscle, insulin-degrading protease by dialysis against EDTA, this enzyme was reactivated fully (greater than 80%) by a 100 microM concentration of free Ca2+. These observations identify a previously unrecognized but important influence of calcium on cellular insulin handling and provide further evidence for a major role of the calcium-activated enzyme, insulin protease, in cellular insulin degradation.
mesh_terms: D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D004492:Edetic Acid / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000494:pharmacology; D009132:Muscles / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
chemical_list: D007328:Insulin; D001464:Barium; D008345:Manganese; D005934:Glucagon; D004492:Edetic Acid; D008274:Magnesium; D002118:Calcium