Glucose regulation of β-cell stress in type 2 diabetes

G. Leibowitz*, E. Bachar, M. Shaked, A. Sinai, M. Ketzinel-Gilad, E. Cerasi, N. Kaiser

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


In type 2 diabetes, the β-cell is exposed to chronic hyperglycaemia, which increases its metabolic activity, with excess generation of reactive oxygen species (ROS) as a consequence. ROS accumulation induces both oxidative and endoplasmic reticulum (ER) stress, which may lead to β-cell dysfunction and apoptosis. Recent data suggest that oxidative and ER stress are interconnected, although the mechanisms involved in nutrient regulation of the different stress pathways are dissimilar. Several components of the oxidative and ER stress machineries have important roles in the physiological response to glucose and are thus necessary for normal β-cell function. Glucose stimulates signalling pathways that provide crucial messages for β-cell adaptation to metabolic stress; however, the same pathways may eventually lead to apoptosis. Dynamic, temporally fluctuating activation of stress signalling is probably required for the maintenance of β-cell survival, whereas its persistent activation results in β-cell dysfunction and apoptosis. Thus, stress signalling is a 'double-edged sword' that may promote adaptation or apoptosis according to the balance between the divergent outputs of the various pathways. Developing new strategies for β-cell protection based on inhibition of oxidative and/or ER stress requires comprehensive understanding of the switch from β-cell adaptation to β-cell apoptosis under conditions of metabolic stress, such as occurs under hyperglycaemic conditions.

Original languageAmerican English
Pages (from-to)66-75
Number of pages10
JournalDiabetes, Obesity and Metabolism
Issue numberSUPPL. 2
StatePublished - Oct 2010
Externally publishedYes


  • Diabetes
  • ER stress
  • Oxidative stress
  • UPR
  • β-cells


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