Naringenin and falcarinol stimulate glucose uptake and TBC1D1 phosphorylation in porcine myotube cultures

Abstract

Abstract: Insulin resistance in muscles is a major problem associated with Type 2 diabetes. Bioactive compounds of plant origin have long been known for possessing anti-diabetic properties. We have studied the effect of the bioactive compounds naringenin (dihydroflavonol) and falcarinol (polyacetylene) on glucose uptake (GU) in normal and insulin resistant primary porcine myotubes, in the presence and absence of insulin to identify signaling pathways mediating their effects on GU. The dependence on glucose transporter type 4 (Glut4) activity, insulin signaling and AMP-activated protein kinase (AMPK)-signaling was studied by using the Glut4 inhibitor indinavir, the phosphatidyl inositol-3 kinase (PI3K) and p38 mitogen activated protein kinase (MAPK) inhibitor wortmannin, and the AMPK inhibitor dorsomorphin (DM), respectively. Naringenin and falcarinol stimulated GU was attenuated in the presence of indinavir and wortmannin, indicating a dependence on Glut4 activity as well as PI3K and/or p38MAPK activity. By contrast, DM diminished GU induced by naringenin only, indicating that falcarinol-stimulated GU was independent of AMPK activity. Finally, we show that naringenin and falcarinol enhance phosphorylation of TBC1D1 suggesting that these compounds enhance translocation of Glut4 containing vesicles and thereby GU via a TBC1D1-dependent mechanism