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01-06-2018 | Article

Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes

Authors: Cynthia M. F. Monaco, Meghan C. Hughes, Sofhia V. Ramos, Nina E. Varah, Christian Lamberz, Fasih A. Rahman, Chris McGlory, Mark A. Tarnopolsky, Matthew P. Krause, Robert Laham, Thomas J. Hawke, Christopher G. R. Perry

Published in: Diabetologia | Issue 6/2018

Abstract

Aims/hypothesis

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.

Methods

Physically active, young adults (men and women) with type 1 diabetes (HbA_1c 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.

Results

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-AMPKα^Thr172), and its downstream targets, phosphorylated Unc-51 like autophagy activating kinase 1 (p-ULK1^Ser555) and p62, was similar between groups. In addition, no differences in muscle capillary density or platelet aggregation were observed between the groups.

Conclusions/interpretation

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.

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Title: Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes
Authors: Cynthia M. F. Monaco
Meghan C. Hughes
Sofhia V. Ramos
Nina E. Varah
Christian Lamberz
Fasih A. Rahman
Chris McGlory
Mark A. Tarnopolsky
Matthew P. Krause
Robert Laham
Thomas J. Hawke
Christopher G. R. Perry
Publication date: 01-06-2018
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 6/2018
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-018-4602-6

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Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

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Abstract

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Conclusions/interpretation

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