Attenuation of Armanni-Ebstein lesions in a rat model of diabetes by a new anti-fibrotic, anti-inflammatory agent, FT011.

Abstract:

AIMS/HYPOTHESIS:A key morphological feature of diabetic nephropathy is the accumulation and deposition of glycogen in renal tubular cells, known as Armanni-Ebstein lesions. While this observation has been consistently reported for many years, the molecular basis of these lesions remains unclear. METHODS:Using biochemical and histochemical methods, we measured glycogen concentration, glycogen synthase and glycogen phosphorylase enzyme activities, and mRNA expression and protein levels of glycogenin in kidney lysates from control and transgenic (mRen-2)27 rat models of diabetes that had been treated with and without a new anti-fibrotic agent, FT011. RESULTS:Diabetic nephropathy was associated with increased glycogen content, increased glycogen synthase activity and decreased glycogen phosphorylase activity. Glycogenin, the key protein responsible for initiating the synthesis of each glycogen particle, had very high levels in the diabetic kidney together with increased mRNA expression compared with control kidneys. Treatment with FT011 did not change glycogen synthase or glycogen phosphorylase enzyme activities but prevented both glycogenin mRNA synthesis and accumulation of Armanni-Ebstein lesions in the diabetic kidney. CONCLUSIONS/INTERPRETATION:Armanni-Ebstein lesions found in diabetic nephropathy are due to aberrant glycogenin protein levels and mRNA expression, providing an explanation for the increased glycogen concentration found within the diabetic kidney. FT011 treatment in diabetic rats reduced glycogenin levels and, subsequently, renal glycogen concentration.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Lau X,Zhang Y,Kelly DJ,Stapleton DI

doi

10.1007/s00125-012-2805-9

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

675-9

issue

3

eissn

0012-186X

issn

1432-0428

journal_volume

56

pub_type

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