Insulin-sensitizing and insulin-mimetic activities of Sarcopoterium spinosum extract

Ethnopharmacological relevance Sarcopoterium spinosum is an abundant plant in Israel, used by Bedouin medicinal practitioners for the treatment of diabetes. In our previous study we validated the anti-diabetic activity of Sarcopoterium spinosum. The aim of this study was to further clarify its mechanism of action. Materials and methods In-vivo studies were performed on KK-a/y mice given the extract for 6 weeks. Insulin tolerance test was performed, and relative pancreatic islets area was measured. Mechanisms of action were investigated in L6 myotubes using protein array, Western blot analysis and confocal microscopy. Glucose uptake assays were performed in 3T3-L1 adipocytes. Results Sarcopoterium spinosum extract reduced fasting blood glucose and improved insulin sensitivity in treated mice. Hypertrophic islets were detected in diabetic, but not in Sarcopoterium spinosum-treated mice. Sarcopoterium spinosum phosphorylated PTEN on ser380 and thr382/383, which are known inhibitory sites. PKB was not phosphorylated by Sarcopoterium spinosum, however, translocation of PKB from cytoplasm to the membrane and nucleus was detected. Target proteins of PKB were regulated by Sarcopoterium spinosum; GSK3β was phosphorylated and cytosolic localization of FoxO was increased. Glucose uptake was increased in a PI3K and AMPK-independent mechanism. Conclusions We suggest that Sarcopoterium spinosum inhibited PTEN and activated PKB by a mechanism which is independent of ser473 and thr308 phosphorylation. Other post translation modifications might be involved and should be analyzed further in order to understand this unique PKB activation. Identifying the active molecules in the extract, may lead to the development of new agents for the treatment of insulin resistance.