Elevation of Global O-GlcNAc in Rodents Using a Selective O-GlcNAcase Inhibitor Does Not Cause Insulin Resistance or Perturb Glucohomeostasis

Matthew S. Macauley, Xiaoyang Shan, Scott A. Yuzwa, Tracey M. Gloster, David J. Vocadlo

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)949-958
Number of pages10
JournalChemistry and Biology
Volume17
Issue number9
DOIs
Publication statusPublished - 24 Sept 2010

Keywords

  • LINKED N-ACETYLGLUCOSAMINE
  • IN-VIVO
  • 3T3-L1 ADIPOCYTES
  • EUGLYCEMIC CLAMP
  • OXIDATIVE STRESS
  • TAY-SACHS
  • GLUCOSE
  • RATS
  • PUGNAC
  • CELLS

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