By the same authors

From the same journal

Inhibition of O-GlcNAcase Using a Potent and Cell-Permeable Inhibitor Does Not Induce Insulin Resistance in 3T3-L1 Adipocytes

Research output: Contribution to journalArticle

Published copy (DOI)

Author(s)

Department/unit(s)

Publication details

JournalChemistry & Biology
DatePublished - 24 Sep 2010
Issue number9
Volume17
Number of pages12
Pages (from-to)937-948
Original languageEnglish

Abstract

To probe increased O-GlcNAc levels as an independent mechanism governing insulin resistance in 3T3-L1 adipocytes, a new class of O-GlcNAcase (OGA) inhibitor was studied. 6-Acetamido-6-deoxy-castanospermine (6-Ac-Cas) is a potent inhibitor of OGA. The structure of 6-Ac-Cas bound in the active site of an OGA homolog reveals structural features contributing to its potency. Treatment of 3T3-L1 adipocytes with 6-Ac-Cas increases O-GlcNAc levels in a dose-dependent manner. These increases in O-GlcNAc levels do not induce insulin resistance functionally, measured using a 2-deoxyglucose (2-DOG) uptake assay, or at the molecular level, determined by evaluating levels of phosphorylated IRS-1 and Akt. These results, and others described, provide a structural blueprint for improved inhibitors and collectively suggest that increased O-GlcNAc levels, brought about by inhibition of OGA, does not by itself cause insulin resistance in 3T3-L1 adipocytes.

    Research areas

  • BETA-N-ACETYLGLUCOSAMINIDASE, PROTEIN MODIFICATION, GLYCOSYL HYDROLASES, NAG-THIAZOLINE, IN-VIVO, GLUCOSE, PHOSPHORYLATION, PUGNAC, STATE, GLCNACYLATION

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations