RESUMO
PURPOSE: The aim of this work was to assess the effect(s) of de novo ceramide synthesis inhibition on lipid metabolism in skeletal muscle tissue of type 1 diabetic rats. The latter seems to be of vital importance, since previous works have shown its positive influence on lipid metabolism and glucose homeostasis in the case of its counterpart - type 2 diabetes. MATERIALS/METHODS: The animals were randomly assigned to one of the following groups: C - control, M - myriocin (ceramide de novo synthesis inhibitor), D - diabetes (induced by streptozotocin injections); D+M - diabetes+myriocin. We have evaluated intracellular concentration of key sphingolipid species, via chromatography (GC and HPLC), and the activity of their most important enzymes, using radiometric approach. The aforementioned assessments were evaluated in respect to the three different types of muscle tissue representing different spectra of muscle metabolism (soleus - oxidative, red gastrocnemious - oxidative-glycolytic, white gastrocnemious - glycolytic). RESULTS: Interestingly, our therapeutic intervention not only lowered the level of ceramide, its precursors (sphinganine) and derivatives (sphingosine and sphingosine-1-phosphate), but also reduced other lipid species (triacylglycerols, diacylglycerols and free fatty acids) content, thus improving glucose homeostasis in type 1 diabetic animals. CONCLUSIONS: In the light of the results ensuing from this study, it seems conceivable that the reduction of intramuscular ceramide production and accumulation could bestow an insulin-sensitizing effect. If so, then SPT inhibition could find potential future applications as a therapeutic intervention aimed to mitigate the effects of insulin resistance.
