Abstract
The onset and progression of diabetes mellitus type 2 is highly contingent on the amount of functional beta-cell mass. An underlying cause of beta-cell decay in diabetes is oxidative stress, which markedly affects the insulin producing pancreatic cells due to their poor antioxidant defence capacity. Consequently, disturbances of cellular redox signaling have been implicated to play a major role in beta-cell loss in diabetes mellitus type 2. There is evidence suggesting that the glutaredoxin (Grx) system exerts a protective role for pancreatic islets, but the exact mechanisms have not yet been elucidated. In this study, a mouse model for diabetes mellitus type 2 was used to gain further insight into the significance of Grx for the islets of Langerhans in the diabetic metabolism. We have observed distinct differences in the expression levels of Grx in pancreatic islets between obese, diabetic db mice and lean, non-diabetic controls. This finding is the first report about a decrease of Grx expression levels in pancreatic islets of diabetic mice which was accompanied by declining insulin secretion, increase of reactive oxygen species (ROS) production level, and cell cycle alterations. These data demonstrate the essential role of the Grx system for the beta-cell during metabolic stress which may provide a new target for diabetes mellitus type 2 treatment.
Highlights
Diabetes mellitus type 2 is hallmarked by a progressive loss of functional beta-cell mass
Oxidative stress and impaired redox signaling play a pivotal role in beta-cell decay [4]
The leptin-resistant db mouse was employed for investigation of glutaredoxins in diabetes
Summary
Diabetes mellitus type 2 is hallmarked by a progressive loss of functional beta-cell mass. As stress levels exceed the beta-cell’s coping capacity, insulin secretion fades [2, 3]. Oxidative stress and impaired redox signaling play a pivotal role in beta-cell decay [4]. The redox regulation of cellular processes ensures cell viability and function [5]. A major actor in redox signaling and maintenance of redox balance is the glutaredoxin (Grx) system. It consists of NAPDH, glutathione, glutathione reductase and the oxidoreductase glutaredoxin. Its influence on cellular processes is based on reversible post-translational de-glutathionylation of their target’s cysteine residues. There are four glutaredoxins, characterized as mono- or dithiol
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