Functional Deficiencies of Subsarcolemmal Mitochondria in the Type 2 Diabetic
Human Heart.
Authors Croston TL, Thapa D, Holden AA, Tveter KJ, Lewis SE, Shepherd DL, Nichols CE,
Long DM, Olfert IM, Jagannathan R, Hollander JM
Submitted By Submitted Externally on 5/5/2014
Status Published
Journal American journal of physiology. Heart and circulatory physiology
Year 2014
Date Published 4/28/2014
Volume : Pages 307 : H54 - H65
PubMed Reference 24778174
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 non-diabetic and type 2 diabetic patients were examined.
Complex I- and fatty acid-mediated mitochondrial respiration rates were
decreased in diabetic SSM as compared to non-diabetic (P < 0.05 for both), with
no change in IFM. Electron transport chain (ETC) complexes I and IV activities
were decreased in diabetic SSM as compared to non-diabetic (P < 0.05 for both),
with a concomitant decline in their levels (P < 0.05 for both). Regression
analyses comparing co-morbidities determined that diabetes mellitus was the
primary factor accounting for mitochondrial dysfunction. Linear spline models
examining correlative risk for mitochondrial dysfunction indicated that diabetic
patients display the same degree of state 3 and ETC 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 type 2 diabetic patients
and the degree of dysfunction is consistent regardless of the extent of elevated
HbA1c or blood glucose levels.

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