Participation of protein kinases in the stimulant action of GLP-1 on 2-deoxy-D-glucose uptake by normal rat skeletal muscle

Several protein kinases were recently proposed for involvement in GLP-1-stimulated D-glucose transport in skeletal muscle from both normal subjects and type 2 diabetic patients. This study was mainly aimed at investigating the effect of potential inhibitors of distinct protein kinases and protein phosphatase-1 upon insulin- and GLP-1-stimulated 2-deoxy-D-glucose net uptake by normal rat skeletal muscle. The basal uptake of the D-glucose analog was decreased by wortmannin - a phosphatidylinositol-3-kinase inhibitor -, PD98059 - a mitogen-activated protein kinases inhibitor -, and TNFα - a protein phosphatase-1 inhibitor -, but not by either rapamycin - a p70s6 kinase inhibitor -, or H-7 -, a protein kinase C inhibitor -. The enhancing action of both insulin and GLP-1 upon 2-deoxy-D-glucose transport was abolished by PD98059 and H-7, but largely unaffected by TNFα. Wortmannin and rapamycin preferentially affected the response to GLP-1 and insulin, respectively. These findings thus document both analogies and dissimilarities in the participation of the concerned enzymes in the stimulant action of insulin versus GLP-1 upon D-glucose transport in normal rat skeletal muscle. © Georg Thieme Verlag KG Stuttgart.