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Intramuscular heat shock protein 72 and heme oxygenase-1 mRNA are reduced in patients with type 2 diabetes: evidence that insulin resistance is associated with a disturbed antioxidant defense mechanism
journal contribution
posted on 2003-01-01, 00:00 authored by Clinton BruceClinton Bruce, A Carey, J Hawley, M FebbraioTo examine whether genes associated with cellular defense against oxidative stress are associated with insulin sensitivity, patients with type 2 diabetes (n = 7) and age-matched (n = 5) and young (n = 9) control subjects underwent a euglycemic-hyperinsulinemic clamp for 120 min. Muscle samples were obtained before and after the clamp and analyzed for heat shock protein (HSP)72 and heme oxygenase (HO)-1 mRNA, intramuscular triglyceride content, and the maximal activities of β-hyroxyacyl-CoA dehydrogenase (β-HAD) and citrate synthase (CS). Basal expression of both HSP72 and HO-1 mRNA were lower (P < 0.05) by 33 and 55%, respectively, when comparing diabetic patients with age-matched and young control subjects, with no differences between the latter groups. Both basal HSP72 (r = 0.75, P < 0.001) and HO-1 (r = 0.50, P < 0.05) mRNA expression correlated with the glucose infusion rate during the clamp. Significant correlations were also observed between HSP72 mRNA and both β-HAD (r = 0.61, P < 0.01) and CS (r = 0.65, P < 0.01). HSP72 mRNA was induced (P < 0.05) by the clamp in all groups. Although HO-1 mRNA was unaffected by the clamp in both the young and age-matched control subjects, it was increased (P < 0.05) ∼70-fold in the diabetic patients after the clamp. These data demonstrate that genes involved in providing cellular protection against oxidative stress are defective in patients with type 2 diabetes and correlate with insulin-stimulated glucose disposal and markers of muscle oxidative capacity. The data provide new evidence that the pathogenesis of type 2 diabetes involves perturbations to the antioxidant defense mechanism within skeletal muscle.
History
Journal
DiabetesVolume
52Issue
9Pagination
2338 - 2345Publisher
American Diabetes AssociationLocation
Alexandria, VaPublisher DOI
ISSN
0012-1797eISSN
1939-327XLanguage
engPublication classification
C1.1 Refereed article in a scholarly journalUsage metrics
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Citrate synthaseCritical thresholdDual-energy X-ray absorptiometryFree fatty acidFat-free massGlucose disposal rateβ-hyroxyacyl-CoA dehydrogenaseHeme oxygenaseHeat shock proteinIntramuscular triglyceridec-Jun NH2-terminal kinaseMyeloperoxidaseNitric oxide synthasePeroxisome proliferator–activated receptorReactive oxygen speciesTumor necrosis factorScience & TechnologyLife Sciences & BiomedicineEndocrinology & MetabolismHUMAN SKELETAL-MUSCLEOXIDATIVE STRESSFATTY-ACIDSFIBER-TYPETNF-ALPHAEXPRESSIONOBESITYHSP72GENEAVAILABILITY
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