Glucose-induced metabolic memory in Schwann cells: Prevention by PPAR agonists

Esther S. Kim, Fumiko Isoda, Irwin J. Kurland, Charles V. Mobbs

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A major barrier in reversing diabetic complications is that molecular and pathologic effects of elevated glucose persist despite normalization of glucose, a phenomenon referred to as metabolic memory. In the present studies we have investigated the effects of elevated glucose on Schwann cells, which are implicated in diabetic neuropathy. Using quantitative PCR arrays for glucose and fatty acid metabolism,wehave found that chronic (>8 wk) 25mMhigh glucose induces a persistent increase in genes that promote glycolysis, while inhibiting those that oppose glycolysis and alternate metabolic pathways such as fatty acid metabolism, the pentose phosphate pathway, and trichloroacetic acid cycle. These sustained effects were associated with decreased peroxisome proliferator-activated receptor (PPAR)γ bindingandpersistently increased reactive oxygen species, cellular NADH, and altered DNA methylation. Agonists of PPARγ and PPARα prevented select effects of glucose-induced gene expression. These observations suggest that Schwann cells exhibit features of metabolic memory that may be regulated at the transcriptional level. Furthermore, targeting PPAR may prevent metabolic memory and the development of diabetic complications.

Original languageEnglish (US)
Pages (from-to)3054-3066
Number of pages13
JournalEndocrinology
Volume154
Issue number9
DOIs
StatePublished - Sep 1 2013

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Peroxisome Proliferator-Activated Receptors
Schwann Cells
Glucose
Glycolysis
Diabetes Complications
Fatty Acids
Pentose Phosphate Pathway
Trichloroacetic Acid
Diabetic Neuropathies
DNA Methylation
Metabolic Networks and Pathways
NAD
Reactive Oxygen Species
Gene Expression
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Endocrinology

Cite this

Glucose-induced metabolic memory in Schwann cells : Prevention by PPAR agonists. / Kim, Esther S.; Isoda, Fumiko; Kurland, Irwin J.; Mobbs, Charles V.

In: Endocrinology, Vol. 154, No. 9, 01.09.2013, p. 3054-3066.

Research output: Contribution to journalArticle

Kim, Esther S. ; Isoda, Fumiko ; Kurland, Irwin J. ; Mobbs, Charles V. / Glucose-induced metabolic memory in Schwann cells : Prevention by PPAR agonists. In: Endocrinology. 2013 ; Vol. 154, No. 9. pp. 3054-3066.
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