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Elevation of Global O-GlcNAc in rodents using a selective O-GlcNAcase inhibitor does not cause insulin resistance or perturb glucohomeostasis.
- Source :
-
Chemistry & biology [Chem Biol] 2010 Sep 24; Vol. 17 (9), pp. 949-58. - Publication Year :
- 2010
-
Abstract
- The O-GlcNAc modification is proposed to be a nutrient sensor with studies suggesting that global increases in O-GlcNAc levels cause insulin resistance and impaired glucohomeostasis. We address this hypothesis by using a potent and selective inhibitor of O-GlcNAcase, known as NButGT, in a series of in vivo studies. Treatment of rats and mice with NButGT, for various time regimens and doses, dramatically increases O-GlcNAc levels throughout all tissues but does not perturb insulin sensitivity or alter glucohomeostasis. NButGT also does not affect the severity or onset of insulin resistance induced by a high-fat diet. These results suggest that pharmacological increases in global O-GlcNAc levels do not cause insulin resistance nor do they appear to disrupt glucohomeostasis. Therefore, the protective benefits of elevated O-GlcNAc levels may be achieved without deleteriously affecting glucohomeostasis.<br /> (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Bridged Bicyclo Compounds, Heterocyclic chemistry
Enzyme Inhibitors chemistry
G(M2) Ganglioside metabolism
Mice
Rats
Rats, Sprague-Dawley
Signal Transduction
beta-N-Acetylhexosaminidases metabolism
Acetylglucosamine metabolism
Bridged Bicyclo Compounds, Heterocyclic pharmacology
Enzyme Inhibitors pharmacology
Glucose metabolism
Insulin Resistance
beta-N-Acetylhexosaminidases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1301
- Volume :
- 17
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Chemistry & biology
- Publication Type :
- Academic Journal
- Accession number :
- 20851344
- Full Text :
- https://doi.org/10.1016/j.chembiol.2010.07.005