ENDOTHELIN MOBILIZES CALCIUM AND ENHANCES GLUCOSE-UPTAKE IN CULTURED HUMAN SKELETAL MYOBLASTS AND L6 MYOTUBES

In this study we used endothelin as a paradigm to explore the concept that some vasoactive agents, acting through mobilization of Ca2+ and s timulation of protein kinase C, can interact with human skeletal muscl e and modify its glucose transport. Cultured human skeletal myoblasts from the vastus lateralis demonstrated two subclasses of high-affinity endothelin receptors and a robust increase in cytosolic free Ca2+ upo n exposure to endothelin. The endothelin-evoked rise in cytosolic free Ca2+ primarily resulted from Ca2+ mobilization from intracellular org anelles. Both endothelin and insulin enhanced [H-3]deoxy-D-glucose upt ake in human myoblasts, but their effects were not additive. These fin dings also were observed in differentiated myotubes of L6 skeletal mus cle cells. Moreover, [H-3]deoxy-D-glucose uptake in human myoblasts wa s enhanced by treatment with phorbol 12-myristate 13-acetate. The endo thelin- and insulin-mediated increases in [H-3]deoxy-D-glucose were to tally ablated by treatment with calphostin C. Such observations sugges t that endothelin can enhance glucose uptake in human skeletal muscle. This is mediated through mechanisms that are at least partially prote in kinase C dependent. Thus, increased levers of endothelin in vascula r beds may contribute to altered glucose metabolism in essential hyper tension.