Effects of Streptozotocin-induced Diabetes and Elevation of Plasma FFA on Ceramide Metabolism in Rat Skeletal Muscle

Abstract

Ceramide is likely to mediate in induction of insulin resistance. The aim of the present study was to examine the effect of streptozotocin-diabetes and treatment with heparin on ceramide metabolism in skeletal muscles. The experiments were performed on Wistar rats divided into three groups: 1) control, 2) treated with streptozotocin, and 3) treated with heparin. Assays were carried out on three types of muscle: slow-twitch oxidative (soleus), fast-twitch oxidative-glycolytic, and fast-twitch glycolytic (red and white section of the gastrocnemius, respectively). The activity of serine palmitoyltransferase (SPT), neutral and acid sphingomyelinase (nSMase and aSMase), and neutral and alkaline ceramidase (nCDase and alCDase) was examined. The content of ceramide, sphinganine, sphingosine, and sphingosine-1-phosphate was also measured. Both streptozotocin-diabetes and treatment with heparin increased the activity of SPT in each type of muscle. Heparin inhibits the activity of aSMase and concomitantly induces the activity of nSMase in each studied muscle. Streptozotocin decreased aSMase activity in each muscle and increased nSMase activity in the soleus and red section of the gastrocnemius. Heparin induced, whereas streptozotocin inhibited the activity of n-CDase in the soleus and the red section of the gastrocnemius. Heparin increased the activity of alCDase in the red gastrocnemius. In the soleus and the white gastrocnemius the activity of alCDase decreased. Streptozotocin significantly increased the content of ceramide in each muscle studied and heparin did it only in the soleus. It is concluded that insulin deficiency is accompanied by alterations in ceramide metabolism in skeletal muscles. Increased concentration of the plasma free fatty acids may mediate certain effects of insulin deficiency.