Antihypertensive peptide purified from Styela clava flesh tissue stimulates glucose uptake through AMP-activated protein kinase (AMPK) activation in skeletal muscle cells

Previously, our group described an antihypertensive peptide (Ala-His-Ile-Ile-Ile, MW: 565.3 Da) with angiotensin I-converting enzyme inhibitory and vasodilatory effects that was purified from Styela clava flesh tissue. In the present study, we investigated the metabolic effects of the antihypertensive peptide in skeletal muscle cells. We found that the antihypertensive peptide stimulated glucose uptake in differentiated L6 rat myoblast cells in a dose-dependent manner. Inhibition of AMP-activated protein kinase (AMPK) by compound C significantly inhibited the antihypertensive peptide-stimulated glucose uptake. Western blotting analyses revealed that the antihypertensive peptide stimulated AMPK phosphorylation and this enhancement could be specifically inhibited by compound C. Furthermore, the current study demonstrates that translocation of glucose transporter-4 (GLUT4) to the plasma membrane was stimulated by the antihypertensive peptide. In summary, the findings from this study suggest that the antihypertensive peptide may have beneficial effects on the glucose metabolism in skeletal muscle cells via a mechanism involving AMPK and possible stimulation of the intrinsic activity of GLUT4 transporter.