新たなインスリン抵抗性発症機序の電子顕微鏡による解析

概要

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Insulin resistance in adipocytes induced by tumor necrosis factorα (TNFα) has been analyzed by immunoelectron microscopy with special attention to the interaction between insulin receptor (IR) and ganglioside GM3 in plasma membranes. in normal adipocytes, most of the gold particles of GM3 molecules localized in the plane region with cluster farmation and a small number of GM3 was detected in the surrounding area of caveolae. IR molecules were detected in caveolae region about 19% and the rest of IR were foundin the plane region.The relative raito of IR molecules localized in caveolae was greatly reduced by 20% when the state of insulin resistance was induced by TNFα,in which the amounts of GM3 in plasma membranes were up-regulated.Previoustry,we demonstrated that an inhibitor of ganglioside biosynthesis,D-threo-1-phenyl-2-decanoylamino-3-morphrlino-1-propanol(D-PDMP),could normalize the impaired insulin signaling by blocking the increase of GM3 by TNFα.Here we could show that the decrease of IR molecules in caveolae region by TNFα was restored by D-PDMP.These observation strongly supports our working hypothesis concerning a new pathological feature of insulin resistance.
東北薬科大学の論文