Does the glucose-dependent insulin secretion mechanism itself cause oxidative stress in pancreatic beta-cells?

Abstract:

: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.

journal_name

Diabetes

journal_title

Diabetes

authors

Fridlyand LE,Philipson LH

doi

10.2337/diabetes.53.8.1942

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

1942-8

issue

8

eissn

0012-1797

issn

1939-327X

pii

53/8/1942

journal_volume

53

pub_type

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