ULTRASTRUCTURAL, HISTOCHEMICAL, AND MORPHOMETRIC ANALYSIS OF SKELETAL-MUSCLE IN A MURINE MODEL OF TYPE-I DIABETES

Background. Since peripheral nerves are damaged in diabetes mellitus, morphological changes occur within the diabetic muscle in response to the diabetic neuropathy. The aim of this study was to examine the exte nsor digitorum longus (EDL) from a 42-day streptozotocin-induced diabe tic Swiss Webster mouse (STZ) and compare the muscle morphology and hi stochemistry to age-matched, nondiabetic controls. Methods. The EDL wa s evaluated using electron microscopy in order to investigate the morp hological integrity of the myofibers and neuromuscular junctions. Hist ochemical analysis was completed using the myofibrillar CA+ +-ATPase r eaction of Doriguzzi et al. (1983. Histochemistry, 79:289-294) for use in computer-assisted morphometric analysis of fiber size using Bioqua nt System 4 software.Results. Ultrastructural analysis of the diabetic EDL (N = 5, 225 myofibers/animal) showed a significant number of abno rmal myofibers, exhibiting various degrees of degeneration, signs of d enervation, and necrosis. The STZ myofibers exhibited excessive lipid accumulations and abnormal mitochondrial arrangements. Histochemical a nalysis of the STZ EDL revealed a significant shift in fiber type prof ile (53.6% type 2A and 46.4% type 2B- STZ myofibers; 47.5% type 2A, 52 .5% type 2B nondiabetic controls). Morphometric analysis of myofiber s ize by fiber type (200 myofibers/muscle/fiber type) indicated a signif icant decrease in myofiber size for both type 2A and type 2B fibers in the STZ diabetic mouse. Conclusion. The degeneration and necrosis of myofibers concomitant with the sever atrophy of both the type 2A and 2 B myofibers in the STZ muscle could account for the functional alterat ions seen in diabetic muscle. (C) 1994 Wiley-Liss, Inc.