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Proteomics and PUGNA city will overcome questioning of insulin resistance induction by nonselective inhibition of O ‐ G lc NA case
Author(s) -
Dehennaut Vanessa,
Lefebvre Tony
Publication year - 2013
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201300363
Subject(s) - insulin resistance , insulin , glycosylation , chemistry , in vivo , biochemistry , proteomics , gene , biology , endocrinology , genetics
PTM s are the ultimate elements that perfect the existence and the activity of proteins. Owing to PTM , not less than 500 millions biological activities arise from approximately 20 000 protein‐coding genes in human. Hundreds of PTM were characterized in living beings among which is a large variety of glycosylations. Many compounds have been developed to tentatively block each kind of glycosylation so as to study their biological functions but due to their complexity, many off‐target effects were reported. Insulin resistance exemplifies this problem. Several independent groups described that inhibiting the removal of O ‐ G lc NA c moieties using O‐(2‐acetamido‐2‐deoxy‐d‐glucopyranosylidene)amino‐ N ‐phenylcarbamate ( PUGNA c), a nonselective inhibitor of the nuclear and cytoplasmic O ‐GlcNAcase, induced insulin resistance both in vivo and ex vivo. The development of potent and highly selective O ‐ G lc NA case inhibitors called into question that elevated O ‐ G lc NA cylation levels are responsible for insulin resistance; these compounds not recapitulating the insulin‐desensitizing effect of PUGNA c. To tackle this intriguing problem, a South Korean group recently combined ATP ‐affinity chromatography and gel‐assisted digestion to identify proteins, differentially expressed upon treatment of 3 T 3‐ L 1 adipocytes with PUGNA c, involved in protein turnover and insulin signaling.