Journal Article

DZNE-2020-06259

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes.

Monaco, C. M. F. ; Hughes, M. C. ; Ramos, S. V. ; Varah, N. E. ; Lamberz, C.DZNE* ; Rahman, F. A. ; McGlory, C. ; Tarnopolsky, M. A. ; Krause, M. P. ; Laham, R. ; Hawke, T. J. (Corresponding author) ; Perry, C. G. R.

2018
Springer Heidelberg

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Please use a persistent id in citations: doi:10.1007/s00125-018-4602-6

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.

Keyword(s): Adult (MeSH) ; Body Mass Index (MeSH) ; Calcium: chemistry (MeSH) ; Diabetes Mellitus, Type 1: metabolism (MeSH) ; Diabetes Mellitus, Type 1: pathology (MeSH) ; Energy Metabolism (MeSH) ; Exercise: physiology (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Hydrogen Peroxide: metabolism (MeSH) ; Insulin: metabolism (MeSH) ; Male (MeSH) ; Microscopy, Electron, Transmission (MeSH) ; Microscopy, Fluorescence (MeSH) ; Mitochondria: metabolism (MeSH) ; Mitochondria: ultrastructure (MeSH) ; Muscle, Skeletal: metabolism (MeSH) ; Muscle, Skeletal: pathology (MeSH) ; Muscle, Skeletal: ultrastructure (MeSH) ; Oxygen Consumption (MeSH) ; Young Adult (MeSH) ; Insulin ; Hydrogen Peroxide ; Calcium

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Contributing Institute(s):

1. Cryo-electron microscopy and tomography (AG Alamoudi)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; IF >= 10 ; JCR ; SCOPUS ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article (Erratum/Correction) Monaco, C. M. F. ; Hughes, M. C. ; Ramos, S. V. ; Varah, N. E. ; Lamberz, C.DZNE* ; Rahman, F. A. ; McGlory, C. ; Tarnopolsky, M. A. ; Krause, M. P. ; Laham, R. ; Hawke, T. J. (Corresponding author) ; Perry, C. G. R.
Correction to: Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes.
Diabetologia 63(4), 887-888 (2020) [10.1007/s00125-020-05092-w]2020 BibTeX | EndNote: XML, Text | RIS

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