Kidney Res Clin Pract.  2014 Mar;33(1):26-32.

Diabetic conditions modulate the adenosine monophosphate-activated protein kinase of podocytes

• Ha TS
• Park HY
• Nam JA
• Han GD

Abstract

BACKGROUND
Adenosine monophosphate-activated protein kinases (AMPKs), as a sensor of cellular energy status, have been known to play an important role in the pathophysiology of diabetes and its complications. Because AMPKs are known to be expressed in podocytes, it is possible that podocyte AMPKs could be an important contributing factor in the development of diabetic proteinuria. We investigated the roles of AMPKs in the pathological changes in podocytes induced by high-glucose (HG) and advanced glycosylation end products (AGEs) in diabetic proteinuria.
METHODS
We prepared streptozotocin-induced diabetic renal tissues and cultured rat and mouse podocytes under diabetic conditions with AMPK-modulating agents. The changes in AMPKalpha were analyzed with confocal imaging and Western blotting under the following conditions: (1) normal glucose (5mM, =control); (2) HG (30mM); (3) AGE-added; or (4) HG plus AGE-added.
RESULTS
The density of glomerularphospho-AMPKalpha in experimental diabetic nephropathy decreased as a function of the diabetic duration. Diabetic conditions including HG and AGE changed the localization of phospho-AMPKalpha from peripheral cytoplasm to internal cytoplasm and peri- and intranuclear areas in podocytes. HG reduced the AMPKalpha (Thr172) phosphorylation of rat podocytes, and similarly, AGEs reduced the AMPKalpha (Thr172) phosphorylation of mouse podocytes. The distributional and quantitative changes in phospho-AMPKalpha caused by diabetic conditions were preventable using AMPK activators, metformin, and 5-aminoimidazole-4-carboxamide-1beta-riboside.
CONCLUSION
We suggest that diabetic conditions induce the relocation and suppression of podocyte AMPKalpha, which would be a suggestive mechanism in diabetic podocyte injury.

Keyword

Adenosine monophosphate-activated protein kinase; Advanced glycosylation end products; Diabetic nephropathy; Podocyte

MeSH Terms

Adenosine*
AMP-Activated Protein Kinases
Animals
Blotting, Western
Cytoplasm
Diabetic Nephropathies
Glucose
Glycosylation End Products, Advanced
Metformin
Mice
Natural Resources
Phosphorylation
Podocytes*
Protein Kinases*
Proteinuria
Rats
AMP-Activated Protein Kinases
Adenosine
Glucose
Glycosylation End Products, Advanced
Metformin
Protein Kinases