mitochondrial dysfunction in type 2 diabetes

[1eye]

International Angiology 2017 Mar 14

DOI: 10.23736/S0392-9590.17.03824-X

Copyright © 2017 EDIZIONI MINERVA MEDICA

language: English
Mitochondrial dysfunction in calf muscles of patients with combined peripheral arterial disease and diabetes type 2

Brian LINDEGAARD PEDERSEN 1✉, Niels BÆKGAARD 1, Bjørn QUISTORFF 2

1 Department of Vascular Surgery, Rigshospitalet, Gentofte Hospital, Gentofte, Denmark; 2 Nuclear Magnetic Resonance Centre, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

BACKGROUND: This study elucidate the effects on muscle mitochondrial function in patients suffering from combined peripheral arterial disease (PAD) and type 2 diabetes (T2D) and the relation to patient symptoms and treatment.
METHODS: Near Infra Red Spectroscopy (NIRS) calf muscle exercise tests were conducted on Forty subjects, 15 (PAD), 15 (PAD+T2D) and 10 healthy age matched controls (CTRL) recruited from the vascular outpatient clinic at Gentofte County Hospital, Denmark. Calf muscle biopsies (~ 80 mg) (Gastrocnemius and Anterior tibial muscles) were sampled and mitochondrial function tested applying high resolution oxygraphy on isolated muscle fibers.
RESULTS: The NIRS exercise tests showed evidence of mitochondrial dysfunction in the PAD+T2D group by a longer recovery of the deoxygenation resulting from exercise in spite of a higher exercise oxygenation level compared to the PAD group. This was confirmed by a ~30% reduction in oxygen consumption in the muscle biopsy tests for the PAD+T2D compared to the PAD group (P<0.05). We claim that this mitochondrial dysfunction partly explains the ~30% reduction in tread mill walking distance for the PAD+T2D group observed in this study.
CONCLUSIONS: These findings support the use of early surgical revascularization in the PAD+T2D group, in order to obtain better walking performance and probably reduced risk of permanent mitochondrial damage.

[1eye]

J Vis Exp. 2017 Feb 8;(120). doi: 10.3791/54985.
High-resolution Respirometry to Assess Mitochondrial Function in Permeabilized and Intact Cells.
Djafarzadeh S1, Jakob SM2.
Author information
Abstract

A high-resolution oxygraph is a device for measuring cellular oxygen consumption in a closed-chamber system with very high resolution and sensitivity in biological samples (intact and permeabilized cells, tissues or isolated mitochondria). The high-resolution oxygraph device is equipped with two chambers and uses polarographic oxygen sensors to measure oxygen concentration and calculate oxygen consumption within each chamber. Oxygen consumption rates are calculated using software and expressed as picomoles per second per number of cells. Each high-resolution oxygraph chamber contains a stopper with injection ports, which makes it ideal for substrate-uncoupler-inhibitor titrations or detergent titration protocols for determining effective and optimum concentrations for plasma membrane permeabilization. The technique can be applied to measure respiration in a wide range of cell types and also provides information on mitochondrial quality and integrity, and maximal mitochondrial respiratory electron transport system capacity.

PMID:
28287504
DOI:
10.3791/54985