A SYNTHETIC PEPTIDE CORRESPONDING TO THE RAB4 HYPERVARIABLE CARBOXYL-TERMINAL DOMAIN INHIBITS INSULIN ACTION ON GLUCOSE-TRANSPORT IN RAT ADIPOCYTES

The present study was conducted to examine the involvement of Rab4, a low molecular weight GTP-binding protein, in the action of insulin on glucose transport, A synthetic peptide corresponding to the Rab4 hyper variable carboxyl-terminal domain, Rab4-(191-210), was successfully tr ansferred into rat adipocytes by electroporation and inhibited insulin -stimulated glucose transport by about 50% without affecting the basal transport activity, In contrast, synthetic peptides corresponding to the Rab3C and Rab3D carboxyl-terminal hypervariable domain had little effect on insulin action on glucose transport, The Rab4-(191-210) pept ide also reduced insulin-induced GLUT4 translocation from the intracel lular pool to the plasma membrane, Furthermore, the Rab4-(191-210) pep tide reduced both insulin-induced glucose transport and GLUT4 transloc ation in the presence of a major histocompatibility complex class I an tigen-derived peptide, D-k-(62-85), which is a potent inhibitor of GLU T4 internalization, suggesting that the peptide inhibited exocytotic r ecruitment of GLUT4-containing vesicles, The Rab4-(191-210) peptide al so inhibited GTP gamma S-stimulated glucose transport, In addition, in sulin-stimulated glucose transport was inhibited by the addition of an ti-Rab4 antibody, These results suggest that Rab4 protein plays a cruc ial role in insulin action on GLUT4 translocation, especially in exocy totic recruitment by the hormone of the glucose transporter to the pla sma membrane from the intracellular retention pool.