Emerging role of Akt kinase/protein kinase B signaling in pathophysiology of diabetes and its complications

J. Ždychovǎ, R. Komers

Research output: Contribution to journalShort survey

147 Scopus citations

Abstract

In addition to a number of deleterious effects on cellular integrity and functions, diabetic metabolic milieu has been implicated in a rapidly growing number of alterations in signal transduction. In this review we focus on Akt kinase physiology, its alterations in diabetes mellitus (DM), and on the emerging role of this signaling system in the pathophysiology of diabetic microvascular complications. Studies focusing on Akt in diabetes suggest both decrease and increase of Akt activity in DM. Alterations of Akt activity have been found in various tissues and cells in diabetes depending on experimental and clinical contexts. There is convincing evidence suggesting defective Akt signaling in the development of insulin resistance. Similar defects, as in insulin-sensitive tissues, have been reported in endothelia of DM Type 2 models, possibly contributing to the development of endothelial dysfunction under these conditions. In contrast, Akt activity is increased in some tissues and vascular beds affected by complications in DM Type 1. Identification of the role of this phenomenon in DM-induced growth and hemodynamic alterations in affected vascular beds remains one of the major challenges for future research in this area. Future studies should include the evaluation of therapeutical benefits of pharmacological modulators of Akt activity.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalPhysiological Research
Volume54
Issue number1
StatePublished - Mar 29 2005

Keywords

  • Akt kinase
  • Diabetes mellitus
  • Diabetic vascular complications
  • Insulin

ASJC Scopus subject areas

  • Physiology

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