Does the glucose-dependent insulin secretion mechanism itself cause oxidative stress in pancreatic beta-cells?
Glucose-dependent insulin secretion (GDIS), reactive oxygen species (ROS) production, and oxidative stress in pancreatic beta-cells may be tightly linked processes. Here we suggest that the same pathways used in the activation of GDIS (increased glycolytic flux, ATP-to-ADP ratio, and intracellular Ca2+ concentration) can dramatically enhance ROS production and manifestations of oxidative stress and, possibly, apoptosis. The increase in ROS production and oxidative stress produced by GDIS activation itself suggests a dual role for metabolic insulin secretagogues, as an initial sharp increase in insulin secretion rate can be accompanied by progressive beta-cell injury. We propose that therapeutic strategies targeting enhancement of GDIS should be carefully considered in light of possible loss of beta-cell function and mass.
Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Leonid E
LE
Fridlyand
Louis H
LH
Philipson
D000818:Animals; D005947:Glucose / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects*
D007328:Insulin; D005947:Glucose