| Popis: |
Background: Features of type 1 diabetes mellitus (T1DM) include impaired skeletal muscle regenerative capacity and accumulation of muscle lipids; however, the influence of lipids remains unknown in regenerating skeletal muscle with T1DM. This study assessed the lipid response in regenerating skeletal muscle following injury. Methods: Wild-type (WT) and T1DM (Akita) mice (n=5) received cardiotoxin (CTX) injections into the left tibialis anterior which were harvested at 5-days post-injury, cryosectioned, and stained to visualize lipids. To determine sphingolipid and enzyme concentrations, WT (n=22) and Akita (n=21) mice received CTX injections into the left quadriceps and gastrocnemius-plantaris-soleus complex which were harvested at 1-, 3-, 5-, and 7-days post-injury (n=4-6). Sphingolipids and enzyme levels were analyzed by liquid chromatography-mass spectrometry (LC-MS) and Western Blotting, respectively. Results: Akita mice displayed increased lipid deposition in injured muscle as compared to uninjured muscle and both conditions of WT muscle. Sphingosine-1-phosphate (S1P) was elevated in injured muscle as compared to uninjured muscle at 5 days post-injury; however, this response was blunted in Akita muscle. Sphingosine lyase (SL) expression was elevated in Akita injured muscle with no changes in sphingosine kinase or ERK1/2 expression. Ceramide-1-phosphate (C1P) was elevated in Akita muscle at 5 days post-injury; however, no differences were detected for ceramide kinase (CerK). Conclusion: These data indicate that at early time points, skeletal muscle regeneration is impaired in T1DM due to accelerated S1P breakdown and accumulation of C1P. The increase in C1P, despite the absence of CerK, change suggests an alternate pathway of ceramide phosphorylation in regenerating muscle. |
