Abnormal
glucose handling has emerged as a major clinical problem in millions of diabetic patients worldwide.
Insulin resistance affects especially one of the main target organs of this
hormone, the skeletal musculature, making impaired
glucose metabolism in contractile fibres a major feature of
type 2 diabetes. High levels of circulating
free fatty acids, an increased intramyocellular
lipid content, impaired
insulin-mediated
glucose uptake, diminished mitochondrial functioning and an overall weakened metabolic flexibility are pathobiochemical hallmarks of diabetic skeletal muscles. In order to increase our cellular understanding of the molecular mechanisms that underlie this complex diabetes-associated skeletal muscle pathology, we initiated herein a mass spectrometry-based proteomic analysis of skeletal muscle preparations from the non-obese Goto-Kakizaki rat model of
type 2 diabetes. Following staining of high-resolution two-dimensional
gels with colloidal
Coomassie Blue, 929
protein spots were detected, whereby 21
proteins showed a moderate differential expression pattern. Decreased
proteins included
carbonic anhydrase,
3-hydroxyisobutyrate dehydrogenase and
enolase. Increased
proteins were identified as
monoglyceride lipase,
adenylate kinase,
Cu/Zn superoxide dismutase,
phosphoglucomutase,
aldolase,
isocitrate dehydrogenase,
cytochrome c oxidase, small heat shock Hsp27/B1, actin and
3-mercaptopyruvate sulfurtransferase. These proteomic findings suggest that the diabetic phenotype is associated with a generally perturbed
protein expression pattern, affecting especially
glucose,
fatty acid,
nucleotide and
amino acid metabolism, as well as the contractile apparatus, the cellular stress response, the
anti-oxidant defense system and detoxification mechanisms. The altered expression levels of distinct skeletal muscle
proteins, as documented in this study, might be helpful for the future establishment of a comprehensive
biomarker signature of
type 2 diabetes. Reliable markers could be used for improving diagnostics, monitoring of
disease progression and therapeutic evaluations.