Croston 2014 Am J Physiol Heart Circ Physiol
Croston TL, Thapa D, Holden AA, Tveter KJ, Lewis SE, Shepherd DL, Nichols CE, Long DM, Olfert IM, Jagannathan R, Hollander JM (2014) Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart. Am J Physiol Heart Circ Physiol 307:H54-65. |
Croston TL, Thapa D, Holden AA, Tveter KJ, Lewis SE, Shepherd DL, Nichols CE, Long DM, Olfert IM, Jagannathan R, Hollander JM (2014) Am J Physiol Heart Circ Physiol
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 β€ 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 β€ 0.05 for both), with a concomitant decline in their levels (P β€ 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.
Labels: MiParea: Respiration
Pathology: Diabetes
Organism: Human Tissue;cell: Heart Preparation: Isolated mitochondria
Coupling state: OXPHOS
Comorbidity