Contractile and metabolic responses of mouse fast- and slow-twitch muscle to streptozotocin-induced diabetes

摘要

Streptozotocin (STZ) diabetes induces complex structural and biochemical changes in mouse skeletal muscle that are time and muscle type dependant. Contractile economy, basal O$sb2$ consumption, and rates of post-tetanic recovery O$sb2$ consumption were measured in fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles from control and STZ-diabetic mice. Rates of PCr recovery were measured only in fast-twitch EDL from control and STZ-diabetic mice. Basal and recovery O$sb2$ consumption were measured polarographically in both muscles at 4, 14, and 35 days post-STZ injection. The normalized O$sb2$ cost of contraction is significantly lower in EDL at 14 and 35 days, post injection, by 14% and 20% respectively. Normalized O$sb2$ cost of contraction is also lower in Sol by 35 days (20%). Normalized basal O$sb2$ consumption is significantly higher in STZ-Sol (27%) by 4 days than control but, both STZ-EDL and STZ-Sol show a significant decrease (23% and 28% respectively) in basal O$sb2$ consumption compared to controls after 35 days. The time constant of recovery O$sb2$ consumption was significantly faster (16% in both muscles) by 4 days, however, after 35 days the time constant for STZ-Sol is significantly slower (22%) than control. Time constants for PCr recovery were obtained from $sp{31}$P NMR measurements of post-tetanic PCr resynthesis. The time constant of PCr recovery for STZ-diabetic EDL is significantly slower then age matched control. Additionally, time constants of PCr recovery from diabetic EDL are consistently slower (30%) as compared time constants of recovery O$sb2$ consumption in age matched diabetic mice. Results of this study are consistent with the theory that the observed functional changes represent an adaptive response to the biochemical changes, as a result of STZ-diabetes in these muscles.