In vivo collagen metabolism in spontaneously diabetic (db/db) mice

To further define the pathogenesis of diabetic connective tissue lesions, collagen synthesis and degradation were measured in vivo in spontaneously diabetic db/db mice. A double isotopic labeling technique, in which 14C-labeled and 3H-labeled proline were injected into the same mouse 7 days apart, was applied. Collagen synthesis and degradation were assessed in skins, intestines, hearts, and kidneys. There were no changes in collagen metabolism in the intestines of the diabetic mice. In all other tissues, collagen degradation was accelerated. Collagen synthesis was decreased in skins, but increased in the hearts and kidneys of the diabetic mice. These tissue-specific changes in collagen metabolism resulted in a net loss of collagen in all tissues examined except intestines. The results of this study provide insight into the mechanisms leading to connective tissue defects occurring in diabetes mellitus.