• Home
  • Search Results
  • Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart.

Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart.

American journal of physiology. Heart and circulatory physiology (2014-04-30)
Tara L Croston, Dharendra Thapa, Anthony A Holden, Kevin J Tveter, Sara E Lewis, Danielle L Shepherd, Cody E Nichols, Dustin M Long, I Mark Olfert, Rajaganapathi Jagannathan, John M Hollander
ABSTRACT

The mitochondrion has been implicated in the development of diabetic cardiomyopathy. Examination of cardiac mitochondria is complicated by the existence of spatially distinct subpopulations including subsarcolemmal (SSM) and interfibrillar (IFM). Dysfunction to cardiac SSM has been reported in murine models of type 2 diabetes mellitus; however, subpopulation-based mitochondrial analyses have not been explored in type 2 diabetic human heart. The goal of this study was to determine the impact of type 2 diabetes mellitus on cardiac mitochondrial function in the human patient. Mitochondrial subpopulations from atrial appendages of patients with and without type 2 diabetes were examined. Complex I- and fatty acid-mediated mitochondrial respiration rates were decreased in diabetic SSM compared with nondiabetic (P ≤ 0.05 for both), with no change in IFM. Electron transport chain (ETC) complexes I and IV activities were decreased in diabetic SSM compared with nondiabetic (P ≤ 0.05 for both), with a concomitant decline in their levels (P ≤ 0.05 for both). Regression analyses comparing comorbidities determined that diabetes mellitus was the primary factor accounting for mitochondrial dysfunction. Linear spline models examining correlative risk for mitochondrial dysfunction indicated that patients with diabetes display the same degree of state 3 and electron transport chain complex I dysfunction in SSM regardless of the extent of glycated hemoglobin (HbA1c) and hyperglycemia. Overall, the results suggest that independent of other pathologies, mitochondrial dysfunction is present in cardiac SSM of patients with type 2 diabetes and the degree of dysfunction is consistent regardless of the extent of elevated HbA1c or blood glucose levels.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MOPS, ≥99.5% (titration)
Sigma-Aldrich
MOPS, BioPerformance Certified, suitable for cell culture, ≥99.5% (titration)
Sigma-Aldrich
MOPS, BioUltra, for molecular biology, ≥99.5% (T)
Sigma-Aldrich
Argon, ≥99.998%
Sigma-Aldrich
MOPS, BioXtra, ≥99.5% (titration)
SAFC
MOPS
Sigma-Aldrich
MOPS, anhydrous, free-flowing, Redi-Dri, ≥99.5%
Sigma-Aldrich
Argon-40Ar, 99.95 atom %