Adverse effects of farnesyltransferase inhibitors on insulin actions

서지정보

ㆍ발행기관 : 충북대학교 동물의학연구소 ㆍ수록지정보 : Journal of Biomedical and Translational Research / 18권 / 3호
ㆍ저자명 : Sun-Ju Yi, Byung Hak Jhun, Kyunghwan Kim

영어 초록

Ras activates a series of downstream effectors, including the mitogen-activated protein kinase pathway and the Rac/Rho pathway after insulin stimulation. Mutations in Ras are found in approximately 30% of all human cancers and are critical factors in tumor initiation and maintenance. There are four Ras proteins with 80-90% amino acid sequence homology with major differences in the carboxyl termini. Ras proteins undergo farnesylation on their carboxyl termini catalyzed by the enzyme protein farnesyltransferase (FTase), which facilitates localization of Ras proteins to the inner surface of the plasma membrane. Because inhibition of FTase would prevent Ras from processing into its active form, FTase is viewed as a potential therapeutic target. A variety of FTase inhibitors have showed great potency against tumor cells in preclinical studies. Although many farnesyltransferase inhibitors have been developed, their adverse effects on the mitogenic and metabolic actions of insulin are not completely understood. Here we show that YH3096, a farnesyltransferase inhibitor, inhibits insulin-mediated DNA synthesis in HIRc-B cells without affecting c-Jun expression and membrane ruffling in HIRc-B cells. Moreover, YH3096 and its derivatives did not affect insulin-induced glucose uptake in 3T3-L1 adipocytes. Our results provide a laboratory evaluation of the effects of Ras inhibitors on insulin functions.

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