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Am J Physiol Endocrinol Metab 296: E422-E432, 2009. First published November 4, 2008; doi:10.1152/ajpendo.90352.2008
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Proteomic changes associated with diabetes in the BB-DP rat

D. Thor Johnson,1,2,3 Robert A. Harris,2 Stephanie French,1 Angel Aponte,1 and Robert S. Balaban1

1Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; 2Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana; and 3Howard Hughes Medical Institute, Bethesda, Maryland

Submitted 10 April 2008 ; accepted in final form 28 October 2008

These studies were structured with the aim of utilizing emerging technologies in two-dimensional (2D) gel electrophoresis and mass spectrometry to evaluate protein expression changes associated with type 1 diabetes. We reasoned that a broad examination of diabetic tissues at the protein level might open up novel avenues of investigation of the metabolic and signaling pathways that are adversely affected in type 1 diabetes. This study compared the protein expression of the liver, heart, and skeletal muscle of diabetes-prone rats and matched control rats by semiquantitative liquid chromatography-mass spectrometry and differential in-gel 2D gel electrophoresis. Differential expression of 341 proteins in liver, 43 in heart, and 9 (2D gel only) in skeletal muscle was detected. These data were assembled into the relevant metabolic pathways affected primarily in liver. Multiple covalent modifications were also apparent in 2D gel analysis. Several new hypotheses were generated by these data, including mechanisms of net cytosolic protein oxidation, formaldehyde generation by the methionine cycle, and inhibition of carbon substrate oxidation via reduction in citrate synthase and short-chain acyl-CoA dehydrogenase.

metabolism; acyl carnitine; citrate synthase; methionine; liver; heart; skeletal muscle; mass spectroscopy; two-dimensional gel electrophoresis


Address for reprint requests and other correspondence: D. T. Johnson, Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Drive, Rm. B1D416, Bethesda, MD 20892-1061 (e-mail: johnsondt{at}nhlbi.nih.gov)




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