EXTRAHEPATIC EXPRESSION OF P450 PROTEINS IN INSULIN-DEPENDENT DIABETES-MELLITUS

1. Male Wistar rats were rendered diabetic by the administration of a single intraperitoneal dose of streptozotocin; the levers of the xenob iotic-inducible P450 proteins were determined in the lung and kidney u sing diagnostic substrates and immunoblotting employing polyclonal ant ibodies. The glutathione conjugation system in the cytosol of these ti ssues was also investigated. 2. The onset of insulin-dependent diabete s did not influence the O-dealkylations of methoxyresorufin, ethoxyres orufin and pentoxyresorufin in either kidney or lung. 3. Lauric acid h ydroxylase activity, however, was induced in the kidney but no activit y was detectable in the lung. Immunoblot analysis of kidney microsomes using antibodies to P4504A1 revealed the presence of two bands, both of which were clearly inducible in diabetes. In pulmonary microsomes a single faint band was detected which also appeared to be higher in th e diabetic rats. 4. Aniline p-hydroxylase activity was not detectable in the kidney, but activity was measurable in the lung and was suppres sed in diabetes. Immunoblot analysis of pulmonary microsomes using ant ibodies to P4502E1 immunodetected a single band which was suppressed i n diabetes. In the kidney microsomes a single band was also detected w hich was, however, markedly elevated in diabetes. 5. Glutathione S-tra nsferase activity was modestly higher in the kidney, but not lung, of the diabetic animals. Glutathione reductase and total glutathione leve ls were not influenced by the presence of diabetes. 6. It is concluded that streptozotocin-induced insulin-dependent diabetes modulates extr ahepatic P450 proteins, the effect being both tissue- and isoform-spec ific.