Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

Sarcopoterium spinosum (S. spinosum) is an abundant plant in Israel, used by Bedouin traditional medicine for the treatment of diabetes. In our previous studies the glucose lowering properties of this herb were validated in vitro and in-vivo. The goal of this study is to clarify the mechanisms of action mediating the effects of S.spinosum on glucose uptake. S. spinosum facilitates glucose uptake by a unique mechanism, different from that induced by either insulin or metformin; S. spinosum increased glucose uptake by 3T3-L1 adipocytes in a mechanism involving Glut4 translocation, independent of AMPK or PI3K activity. Akt activation is required to induce S. spinosum-dependent glucose uptake, however its mechanism of activation is still unclear; while neither ser473 nor thr308 were phosphorylated by S. spinosum, translocation of Akt from cytoplasm to membrane and nucleus was detected. In addition, substrates of Akt were phosphorylated by the extract. The hypothesis that S. spinosum utilizes a different set of proteins to induce glucose uptake was supported by results demonstrating that differentiating adipocytes respond differently to insulin and S. spinosum; while insulin gradually enhanced glucose uptake from the 11th day of differentiation, S. spinosum increased glucose uptake from the 8th day of differentiation. In addition, S. spinosum and insulin had additive effect on glucose uptake in fully differentiated adipocytes. Phosphoproteomics of serine/threonine residues phosphorylated by S. spinosum followed by bioinformatic analysis indicate for the activation of insulin-receptor pathway. We conclude that active ingredients in S. spinosum activate insulin signaling by a unique mechanism. Clarifying this mechanism of action may lead to the development of new agents for the treatment of diabetes.

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