Advanced glycation end product in diabetic rat skeletal muscle in vivo

Background: Advanced glycation end products (AGEs) are implicated in the etiology of diabetic complications in the kidney, nerve and eye. Skeletal muscle contractile parameters have also been found to be altered in diabetes. Glycation has not been extensively studied in skeletal muscle, but AGE-modified proteins may influence contractility. Objective and Methods: The aim of this study was to use immunohistochemistry to identify distribution patterns of the AGE N epsilon-(carboxymethyl)-lysine in plantaris muscle of diabetic rats. Results: Results revealed the presence of N epsilon-(carboxymethyl)lysine intracellularly and also at sites along the myofiber periphery. The number of myofibers immunolabeling for AGE in animals with diabetes was more than 4-fold greater than in control animals. Additionally, there was a greater proportion of slow + fast myosin heavy chain coexpression in the AGE- positive cells from diabetic animals than in AGE-positive fibers from control animals. No significant difference was present between cross-sectional areas of AGE-positive fibers and AGE-negative fibers within the respective experimental groups. Conclusions: AGE accumulation is greater in skeletal muscle in vivo from diabetic animals than in control animals. This AGE accumulation appears to be associated with fiber-type transformation rather than with myofiber size. Further study is needed to determine the identity of these AGE-modified proteins and to determine how they influence skeletal muscle function in diabetes. Copyright (c) 2006 S. Karger AG, Basel.