The role of 5′-AMP-activated protein kinase (AMPK) in diabetic nephropathy: A new direction?

Kevin Wyatt McMahon, Dora I. Zanescu, Vineeta Sood, Elmus G. Beale, Sharma S. Prabhakar

Research output: Contribution to journalArticle

Abstract

Diabetic nephropathy (DN) is a microvascular complication of diabetes that is characterized by proteinuria, glomerulosclerosis, and decreased kidney function ultimately leading to end stage renal disease; in fact, DN is the leading cause of end stage renal disease in the western world. Glycemic and blood pressure control are currently the most common forms of prevention and treatment of the disease. However, despite good glycemic and blood pressure control, many patients still progress to end stage renal disease and require renal replacement therapy, leaving investigators searching for novel DN therapy targets. The AMP-activated protein kinase (AMPK) is a heterotrimeric protein that serves as an energy regulator for the cell. However, numerous extracellular factors that contribute to DN progression (including glucose, vascular endothelial growth factor, insulin, and AngII) may inhibit AMPK activity. Two recent studies indicate that AMPK activity decreases during DN progression (Lee et al. Am J Physiol Renal Physiol 292(2):F617-27 and Cammisotto et al. Am J Physiol Renal Physiol. 294(4):F881-F889). In order to better understand the potential role that AMPK inhibition has in DN, we have reviewed the mechanisms of AMPK regulation, how these regulatory mechanisms are changed in DN, and what effect that might have on AMPK activity. Additionally, we discuss the downstream effects of AMPK signaling, and how diminished AMPK activity would affect these events. We hope that this review may stimulate future research into the beneficial effects of up-regulating AMPK in ameliorating DN.

Original languageEnglish (US)
Pages (from-to)44-50
Number of pages7
JournalCurrent Enzyme Inhibition
Volume5
Issue number1
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

AMP-Activated Protein Kinases
Diabetic Nephropathies
Chronic Kidney Failure
Pressure control
Blood pressure
Kidney
Blood Pressure
Direction compound
Western World
Renal Replacement Therapy
Diabetes Complications
Medical problems
Proteinuria
Vascular Endothelial Growth Factor A
Research Personnel
Insulin
Glucose

Keywords

  • AMPK
  • Diabetic nephropathy
  • Enzyme regulation
  • Molecular pathogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Drug Discovery

Cite this

The role of 5′-AMP-activated protein kinase (AMPK) in diabetic nephropathy : A new direction? / McMahon, Kevin Wyatt; Zanescu, Dora I.; Sood, Vineeta; Beale, Elmus G.; Prabhakar, Sharma S.

In: Current Enzyme Inhibition, Vol. 5, No. 1, 2009, p. 44-50.

Research output: Contribution to journalArticle

McMahon, Kevin Wyatt ; Zanescu, Dora I. ; Sood, Vineeta ; Beale, Elmus G. ; Prabhakar, Sharma S. / The role of 5′-AMP-activated protein kinase (AMPK) in diabetic nephropathy : A new direction?. In: Current Enzyme Inhibition. 2009 ; Vol. 5, No. 1. pp. 44-50.
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