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@ARTICLE{Monaco:139937,
author = {Monaco, Cynthia M F and Hughes, Meghan C and Ramos, Sofhia
V and Varah, Nina E and Lamberz, Christian and Rahman, Fasih
A and McGlory, Chris and Tarnopolsky, Mark A and Krause,
Matthew P and Laham, Robert and Hawke, Thomas J and Perry,
Christopher G R},
title = {{A}ltered mitochondrial bioenergetics and ultrastructure in
the skeletal muscle of young adults with type 1 diabetes.},
journal = {Diabetologia},
volume = {61},
number = {6},
issn = {0012-186X},
address = {Heidelberg},
publisher = {Springer},
reportid = {DZNE-2020-06259},
pages = {1411-1423},
year = {2018},
abstract = {A comprehensive assessment of skeletal muscle
ultrastructure and mitochondrial bioenergetics has not been
undertaken in individuals with type 1 diabetes. This study
aimed to systematically assess skeletal muscle mitochondrial
phenotype in young adults with type 1 diabetes.Physically
active, young adults (men and women) with type 1 diabetes
(HbA1c 63.0 ± 16.0 mmol/mol $[7.9\% ± 1.5\%])$
and without type 1 diabetes (control), matched for sex, age,
BMI and level of physical activity, were recruited
(n = 12/group) to undergo vastus lateralis muscle
microbiopsies. Mitochondrial respiration (high-resolution
respirometry), site-specific mitochondrial H2O2 emission and
Ca2+ retention capacity (CRC) (spectrofluorometry) were
assessed using permeabilised myofibre bundles. Electron
microscopy and tomography were used to quantify
mitochondrial content and investigate muscle ultrastructure.
Skeletal muscle microvasculature was assessed by
immunofluorescence.Mitochondrial oxidative capacity was
significantly lower in participants with type 1 diabetes vs
the control group, specifically at Complex II of the
electron transport chain, without differences in
mitochondrial content between groups. Muscles of those with
type 1 diabetes also exhibited increased mitochondrial H2O2
emission at Complex III and decreased CRC relative to
control individuals. Electron tomography revealed an
increase in the size and number of autophagic remnants in
the muscles of participants with type 1 diabetes. Despite
this, levels of the autophagic regulatory protein,
phosphorylated AMP-activated protein kinase
(p-AMPKαThr172), and its downstream targets, phosphorylated
Unc-51 like autophagy activating kinase 1 (p-ULK1Ser555) and
p62, was similar between groups. In addition, no differences
in muscle capillary density or platelet aggregation were
observed between the groups.Alterations in mitochondrial
ultrastructure and bioenergetics are evident within the
skeletal muscle of active young adults with type 1 diabetes.
It is yet to be elucidated whether more rigorous exercise
may help to prevent skeletal muscle metabolic deficiencies
in both active and inactive individuals with type 1
diabetes.},
keywords = {Adult / Body Mass Index / Calcium: chemistry / Diabetes
Mellitus, Type 1: metabolism / Diabetes Mellitus, Type 1:
pathology / Energy Metabolism / Exercise: physiology /
Female / Humans / Hydrogen Peroxide: metabolism / Insulin:
metabolism / Male / Microscopy, Electron, Transmission /
Microscopy, Fluorescence / Mitochondria: metabolism /
Mitochondria: ultrastructure / Muscle, Skeletal: metabolism
/ Muscle, Skeletal: pathology / Muscle, Skeletal:
ultrastructure / Oxygen Consumption / Young Adult / Insulin
(NLM Chemicals) / Hydrogen Peroxide (NLM Chemicals) /
Calcium (NLM Chemicals)},
cin = {AG Alamoudi},
ddc = {610},
cid = {I:(DE-2719)1013012},
pnm = {341 - Molecular Signaling (POF3-341)},
pid = {G:(DE-HGF)POF3-341},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29666899},
doi = {10.1007/s00125-018-4602-6},
url = {https://pub.dzne.de/record/139937},
}