FoxO proteins in pancreatic β-cells as potential therapeutic targets in diabetes

Abstract

Diabetes results from complete (Type 1) or progressive (Type 2) insulin insufficiency. Resulting chronic and acute hyperglycemia are thus prevented mainly by insulin injections, a therapy that is care intensive, costly and does not abolish vascular damage, with severe consequences for the patient in the long term. In view of the epidemic spread of the disease, diabetes is considered a major threat for public healthcare systems. Thus, there is a great incentive to find therapies and drugs preserving or restoring pancreatic β-cells mass and function. In this context, this review addresses the FoxO transcription factors as direct or indirect, in vivo or ex vivo drug targets, since FoxO proteins play a central role for β-cells growth and resistance to oxidative stress. The review includes specific proposals for preclinical drug development.

Keywords::

• Akt
• β-cell
• diabetes
• drug
• FoxO
• insulin
• islets of Langerhans
• oxidative stress
• PI3K
• transplantation

Financial & competing interests disclosure

Financial support was received from Swiss National Foundation, grants No 310000-116360 and 3100A0–102147/1 to W Schlegel and from the Fondation pour Recherches Médicales, Geneva, Switzerland. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.