Skeletal muscle fiber type switching and atrophy in diabetes mellitus

Abstract

This study demonstrates that switching of mammalian skeletal muscle fibers, identified as to Myosin Heavy Chain (MHC) type, from MHCI to MHCII occurs along with selective MHCII fiber atrophy in Diabetes Mellitus (DM). DM characterized by reduced plasma insulin level was induced by streptozotocin (40 mg/kg body wt STZ in buffer) injection of 6 wk old male Sprague‐Dawley rats; no exogenous insulin was administered. Rats, matched as to birth date and weight, were randomly assigned to test STZ‐DM or Control (injected with buffer only) group; after 3 wks the STZ‐DM (2) and Control rats (2) were sacrificed and their white gastrocnemius (GAST) and soleus (SOL) muscles excised. A 3–5 mm transverse section of each excised muscle was immediately cut and flash frozen (−80°C). The frozen tissue was cut into 12 μm cross‐sections in a cryostat; fibers in cross‐section were stained and identified as to type using 3 different MHC antibodies in serial cross‐sections. For each SOL and GAST cross‐section, 100 contiguous fibers were MHC typed. The proportions and CSA of combined MHCIIa, x/d,b and MHCI (nonhybrid) fibers were analyzed for GAST and SOL, comparing STZ‐DM to Control. MHCI to MHCII type switching in STZ‐DM was significant (p<0.05) only for SOL, although it was evident in GAST. CSA of only the STZ‐DM MHCII fibers was significantly (p<0.05) decreased in both SOL and GAST. Supported by Emory University (SKD) and R01 DK50740‐09 (SRP).