Proteomic changes associated with diabetes in the BB-DP rat

D. Thor Johnson, Robert A. Harris, Stephanie French, Angel Aponte, Robert S. Balaban

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E422-E432
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume296
Issue number3
DOIs
StatePublished - Mar 2009

Keywords

  • Acyl carnitine
  • Citrate synthase
  • Heart
  • Liver
  • Mass spectroscopy
  • Metabolism
  • Methionine
  • Skeletal muscle
  • Two-dimensional gel electrophoresis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

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