Hyperglycemic stress and carbon stress in diabetic glucotoxicity

Xiaoting Luo, Jinzi Wu, Siqun Jing, Liang Jun Yan

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Diabetes and its complications are caused by chronic glucotoxicity driven by persistent hyperglycemia. In this article, we review the mechanisms of diabetic glucotoxicity by focusing mainly on hyperglycemic stress and carbon stress. Mechanisms of hyperglycemic stress include reductive stress or pseudohypoxic stress caused by redox imbalance between NADH and NAD + driven by activation of both the polyol pathway and poly ADP ribose polymerase; the hexosamine pathway; the advanced glycation end products pathway; the protein kinase C activation pathway; and the enediol formation pathway. Mechanisms of carbon stress include excess production of acetyl-CoA that can over-acetylate a proteome and excess production of fumarate that can over-succinate a proteome; both of which can increase glucotoxicity in diabetes. For hyperglycemia stress, we also discuss the possible role of mitochondrial complex I in diabetes as this complex, in charge of NAD + regeneration, can make more reactive oxygen species (ROS) in the presence of excess NADH. For carbon stress, we also discuss the role of sirtuins in diabetes as they are deacetylases that can reverse protein acetylation thereby attenuating diabetic glucotoxicity and improving glucose metabolism. It is our belief that targeting some of the stress pathways discussed in this article may provide new therapeutic strategies for treatment of diabetes and its complications.

Original languageEnglish
Pages (from-to)90-110
Number of pages21
JournalAging and Disease
Volume7
Issue number1
DOIs
StatePublished - Feb 2016

Fingerprint

NAD
Carbon
Diabetes Complications
Proteome
Hyperglycemia
Sirtuins
Hexosamines
Fumarates
Acetyl Coenzyme A
Advanced Glycosylation End Products
Poly(ADP-ribose) Polymerases
Succinic Acid
Acetylation
Protein Kinase C
Oxidation-Reduction
Regeneration
Reactive Oxygen Species
Glucose
Proteins
Therapeutics

Keywords

  • Carbon stress
  • Diabetes
  • Glucotoxicity
  • Hyperglycemic stress
  • Pseudohypoxia
  • Reactive oxygen species
  • Redox imbalance

Cite this

Luo, Xiaoting ; Wu, Jinzi ; Jing, Siqun ; Yan, Liang Jun. / Hyperglycemic stress and carbon stress in diabetic glucotoxicity. In: Aging and Disease. 2016 ; Vol. 7, No. 1. pp. 90-110.
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Hyperglycemic stress and carbon stress in diabetic glucotoxicity. / Luo, Xiaoting; Wu, Jinzi; Jing, Siqun; Yan, Liang Jun.

In: Aging and Disease, Vol. 7, No. 1, 02.2016, p. 90-110.

Research output: Contribution to journalArticle

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