Diabetes mellitus can lead to detrimental consequences on organ systems, including that of skeletal muscle degeneration. A model emulating the effects of type I diabetic insulin deficiency can be created in a murine model using the pharmacological administration of streptozotocin (STZ). When treated with acute STZ, mice undergo rapid weight loss and heightened blood glucose. Components of the insulin/IGF-1 signaling cascade were examined to determine whether protein degradation and protein synthesis mechanisms were altered. PGC-1alpha, a key regulator of metabolism as well as a putative preventor of muscle atrophy was also investigated. To define the role of STZ diabetes on muscle atrophy and altered expression of metabolic genes, several hindlimb muscles of the diabetic mice were examined in parallel. In STZ mice, weight loss was apparent accompanied by decreased muscle weight in the tibialis anterior. By contrast, the muscle weights of the soleus and plantaris were unchanged. As verification of muscle atrophy, molecular markers of atrophy were examined. MuRF1 was unchanged while atrogin-1 mRNA expression increased in the plantaris and tibialis anterior. Akt-2 phosphorylation in the tibialis anterior and plantaris were also decreased, corresponding to the increase in atrogin-1. These results indicate that in early acute STZ diabetes, insulin signaling cascade encourages muscle atrophy in the predominantly glycolytic muscles. In contrast, the soleus displayed decreased expression of PGC-1 at this time period while the plantaris and tibialis anterior remained unaltered. Thus, different muscles respond differently in onset of muscle atrophy as well as metabolic regulation during the early stages of acute STZ diabetes.Diabetes mellitus can lead to detrimental consequences on organ systems, including that of skeletal muscle degeneration.
|Title||:||Muscle Atrophy and Alteration of Metabolic Gene Expression During Early Streptozotocin Induced Diabetes|
|Publisher||:||ProQuest - 2007|