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 stimulation of protein kinase C, can interact with human skeletal muscle 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⁺ upon exposure to endothelin. The endothelin-evoked rise in cytosolic free Ca²⁺ primarily resulted from Ca²⁺ mobilization from intracellular organelles. Both endothelin and insulin enhanced [³H]deoxy-D-glucose uptake in human myoblasts, but their effects were not additive. These findings also were observed in differentiated myotubes of L6 skeletal muscle cells. Moreover, [³H]deoxy-D-glucose uptake in human myoblasts was enhanced by treatment with phorbol 12-myristate 13-acetate. The endothelin- and insulin-mediated increases in [³H]deoxy-D-glucose were totally ablated by treatment with calphostin C. Such observations suggest that endothelin can enhance glucose uptake in human skeletal muscle. This is mediated through mechanisms that are at least partially protein kinase C dependent. Thus, increased levels of endothelin in vascular beds may contribute to altered glucose metabolism in essential hypertension.