Muscle Atrophy and Increased Atrogin‐1 Occur in Fast‐ but not Slow‐Muscle Early in Acute Streptozotocin‐Induced Diabetes

Abstract

The onset of diabetes is characterized by a loss of glucose homeostasis as well as a loss in lean body mass. Recent reports suggest that muscle loss may be fiber type specific and correlated with oxidative capacity (Sandri et al., 2006. PNAS, 103:16260–5). To test this hypothesis a streptozotocin (STZ) ‐treated animal model was used. BALB/c mice were injected with 40 ug/g STZ over the course of 5 days with sham injected controls. Maximal weight loss was observed 5 days post‐injection. Animals were sacrificed at this time and plasma, tibialis anterior (TA) (fast‐twitch), and soleus (SOL) (slow‐twitch), muscles were harvested, weighed and rapidly frozen at −80°C. Plasma glucose levels rose from approximately 150 to 270 mg/dL by day 5. TA muscles decreased in mass from 46 ± 2 to 39 ± 1 mg with no detectable change in SOL weights. Real‐time PCR showed atrogin‐1 mRNA was two‐fold increased in STZ‐treated TA muscles relative to sham‐injected controls but there was no change in SOL expression. Both muscle mass and atrogin‐1 expression show fast‐fiber specific effects under STZ‐treatment that are absent in the more oxidative SOL muscles. These data suggest that oxidative capacity and/or genes controlling oxidative capacity protect against the loss in mass possibly by retarding atrogin‐1 expression.Supported by NIH DK 061184