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Resistance of retinal inflammatory mediators to suppress after reinstitution of good glycemic control: novel mechanism for metabolic memory.

Abstract：

:Diabetic retinopathy resists arrest of its progression after reestablishment of good glycemic control that follows a profound period of poor glycemic control. The objective of this study was to elucidate the role of inflammation in the resistance of retinopathy to arrest after termination of hyperglycemia. Streptozotocin-diabetic rats were (a) maintained either in poor glycemic control [PC group; glycated hemoglobin (GHb)>11%] or in good glycemic control (GC group; GHb<7%) for 12 months or (b) allowed to be in poor glycemic control for 6 months followed by good glycemic control for 6 additional months. At 12 months, retina was analyzed for pro-inflammatory mediators. Twelve months of PC increased retinal interleukin 1beta (IL-1beta) mRNA by 2-fold and its protein expression by 25% compared with the values obtained from normal rat retina. Tumor necrosis factor alpha (TNF-alpha) was elevated approximately 3-fold (both mRNA and protein), and the receptors for IL-1beta and TNF-alpha were increased by 40% each. The concentrations of intercellular cell adhesion molecule 1 and vascular cell adhesion molecule 1 were elevated by 40% and 150%, respectively, and inducible nitric oxide synthase transcripts were elevated by 6-fold. Six months of good glycemic control that followed 6 months of poor glycemic control failed to reverse the elevations in IL-1beta, TNF receptor type I, and intercellular cell adhesion molecule 1 but had some beneficial effects on TNF-alpha, inducible nitric oxide synthase, and vascular cell adhesion molecule 1, however these mediators remained significantly elevated. However, the GC group showed no significant change in the retinal pro-inflammatory mediators compared with the normal rats. Failure to reverse retinal inflammatory mediators supports their important role in the resistance of retinopathy to arrest after cessation of hyperglycemia.

journal_name

J Diabetes Complications

journal_title

Journal of diabetes and its complications

authors

Chan PS,Kanwar M,Kowluru RA

doi

10.1016/j.jdiacomp.2008.10.002

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

55-63

issue

1

eissn

1056-8727

issn

1873-460X

pii

S1056-8727(08)00108-6

journal_volume

24

pub_type

杂志文章

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