Normal to enhanced intrinsic mitochondrial respiration in skeletal muscle of middle- to older-aged women and men with uncomplicated type 1 diabetes
Aims/hypothesis This study interrogated mitochondrial respiratory function and content in skeletal muscle biopsies of healthy adults between 30 and 72 years old with and without uncomplicated type 1 diabetes. Methods Participants (12 women/nine men) with type 1 diabetes (48 ± 11 years of age), witho...
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| creator | Monaco, Cynthia M. F. Tarnopolsky, Mark A. Dial, Athan G. Nederveen, Joshua P. Rebalka, Irena A. Nguyen, Maria Turner, Lauren V. Perry, Christopher G. R. Ljubicic, Vladimir Hawke, Thomas J. |
| description | Aims/hypothesis
This study interrogated mitochondrial respiratory function and content in skeletal muscle biopsies of healthy adults between 30 and 72 years old with and without uncomplicated type 1 diabetes.
Methods
Participants (12 women/nine men) with type 1 diabetes (48 ± 11 years of age), without overt complications, were matched for age, sex, BMI and level of physical activity to participants without diabetes (control participants) (49 ± 12 years of age). Participants underwent a Bergström biopsy of the
vastus lateralis
to assess mitochondrial respiratory function using high-resolution respirometry and citrate synthase activity. Electron microscopy was used to quantify mitochondrial content and cristae (pixel) density.
Results
Mean mitochondrial area density was 27% lower (
p
= 0.006) in participants with type 1 diabetes compared with control participants. This was largely due to smaller mitochondrial fragments in women with type 1 diabetes (−18%,
p
= 0.057), as opposed to a decrease in the total number of mitochondrial fragments in men with diabetes (−28%,
p
= 0.130). Mitochondrial respiratory measures, whether estimated per milligram of tissue (i.e. mass-specific) or normalised to area density (i.e. intrinsic mitochondrial function), differed between cohorts, and demonstrated sexual dimorphism. Mass-specific mitochondrial oxidative phosphorylation (OXPHOS) capacity with the substrates for complex I and complex II (C
I + II
) was significantly lower (−24%,
p
= 0.033) in women with type 1 diabetes compared with control participants, whereas mass-specific OXPHOS capacities with substrates for complex I only (pyruvate [C
I pyr
] or glutamate [C
I glu
]) or complex II only (succinate [C
II succ
]) were not different (
p >
0.404). No statistical differences (
p
> 0.397) were found in mass-specific OXPHOS capacity in men with type 1 diabetes compared with control participants despite a 42% non-significant increase in C
I glu
OXPHOS capacity (
p
= 0.218). In contrast, intrinsic C
I + II
OXPHOS capacity was not different in women with type 1 diabetes (+5%,
p
= 0.378), whereas in men with type 1 diabetes it was 25% higher (
p
= 0.163) compared with control participants. Men with type 1 diabetes also demonstrated higher intrinsic OXPHOS capacity for C
I pyr
(+50%,
p
= 0.159), C
I glu
(+88%,
p
= 0.033) and C
II succ
(+28%,
p
= 0.123), as well as higher intrinsic respiratory rates with low (more physiological) concentrations of either ADP, pyruvate, |
| doi_str_mv | 10.1007/s00125-021-05540-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_34392397</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2561918344</sourcerecordid><originalsourceid>FETCH-LOGICAL-c419t-5638ab05ba0d8d1c3aadb8c3c6bfa52b4572f079ee6ff3d36ff93058dc57ff773</originalsourceid><addsrcrecordid>eNqNkcuKFDEUhoMoTjv6Ai4k4EaQaK51WUrjDQbdKLgrUsnJdMaqpE1SNPMcvrCpqXEEF-ImCcn3_5zwIfSU0VeM0vZ1ppRxRShnhColKWH30I5JwQmVvLuPdus7YV3z7Qw9yvmKUiqUbB6iMyFFz0Xf7tDPTzHNesIlYggHHQxY7ENJPmRv8OxLNIcYbPKVSZCPPuniY6gMzt9hglLv5yWbCXB0lbd2ArK2xclCIvqy9p3iDAHrYPG6n3w54CWYOB8nb3SpQLk-AmbYej1CgfwYPXB6yvDkdj9HX9-9_bL_QC4-v_-4f3NBjGR9IaoRnR6pGjW1nWVGaG3HzgjTjE4rPkrVckfbHqBxTlhR115Q1VmjWufaVpyjF1vvMcUfC-QyzD4bmCYdIC554KphPeuElBV9_hd6FZcU6nSVanvZtC3tKsU3yqSYcwI3HJOfdboeGB1WZcOmbKjKhhtlA6uhZ7fVyziDvYv8dlSBlxtwgjG6bDxUS3dYldp0smeM1xNdJ-3-n977cqNzH5dQalRs0VzxcAnpzyf_Mf8vM23Etg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2579467708</pqid></control><display><type>article</type><title>Normal to enhanced intrinsic mitochondrial respiration in skeletal muscle of middle- to older-aged women and men with uncomplicated type 1 diabetes</title><source>MEDLINE</source><source>SpringerNature Journals</source><source>Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><creator>Monaco, Cynthia M. F. ; Tarnopolsky, Mark A. ; Dial, Athan G. ; Nederveen, Joshua P. ; Rebalka, Irena A. ; Nguyen, Maria ; Turner, Lauren V. ; Perry, Christopher G. R. ; Ljubicic, Vladimir ; Hawke, Thomas J.</creator><creatorcontrib>Monaco, Cynthia M. F. ; Tarnopolsky, Mark A. ; Dial, Athan G. ; Nederveen, Joshua P. ; Rebalka, Irena A. ; Nguyen, Maria ; Turner, Lauren V. ; Perry, Christopher G. R. ; Ljubicic, Vladimir ; Hawke, Thomas J.</creatorcontrib><description>Aims/hypothesis
This study interrogated mitochondrial respiratory function and content in skeletal muscle biopsies of healthy adults between 30 and 72 years old with and without uncomplicated type 1 diabetes.
Methods
Participants (12 women/nine men) with type 1 diabetes (48 ± 11 years of age), without overt complications, were matched for age, sex, BMI and level of physical activity to participants without diabetes (control participants) (49 ± 12 years of age). Participants underwent a Bergström biopsy of the
vastus lateralis
to assess mitochondrial respiratory function using high-resolution respirometry and citrate synthase activity. Electron microscopy was used to quantify mitochondrial content and cristae (pixel) density.
Results
Mean mitochondrial area density was 27% lower (
p
= 0.006) in participants with type 1 diabetes compared with control participants. This was largely due to smaller mitochondrial fragments in women with type 1 diabetes (−18%,
p
= 0.057), as opposed to a decrease in the total number of mitochondrial fragments in men with diabetes (−28%,
p
= 0.130). Mitochondrial respiratory measures, whether estimated per milligram of tissue (i.e. mass-specific) or normalised to area density (i.e. intrinsic mitochondrial function), differed between cohorts, and demonstrated sexual dimorphism. Mass-specific mitochondrial oxidative phosphorylation (OXPHOS) capacity with the substrates for complex I and complex II (C
I + II
) was significantly lower (−24%,
p
= 0.033) in women with type 1 diabetes compared with control participants, whereas mass-specific OXPHOS capacities with substrates for complex I only (pyruvate [C
I pyr
] or glutamate [C
I glu
]) or complex II only (succinate [C
II succ
]) were not different (
p >
0.404). No statistical differences (
p
> 0.397) were found in mass-specific OXPHOS capacity in men with type 1 diabetes compared with control participants despite a 42% non-significant increase in C
I glu
OXPHOS capacity (
p
= 0.218). In contrast, intrinsic C
I + II
OXPHOS capacity was not different in women with type 1 diabetes (+5%,
p
= 0.378), whereas in men with type 1 diabetes it was 25% higher (
p
= 0.163) compared with control participants. Men with type 1 diabetes also demonstrated higher intrinsic OXPHOS capacity for C
I pyr
(+50%,
p
= 0.159), C
I glu
(+88%,
p
= 0.033) and C
II succ
(+28%,
p
= 0.123), as well as higher intrinsic respiratory rates with low (more physiological) concentrations of either ADP, pyruvate, glutamate or succinate (
p
< 0.012). Women with type 1 diabetes had higher (
p
< 0.003) intrinsic respiratory rates with low concentrations of succinate only. Calculated aerobic fitness (Physical Working Capacity Test [PWC
130
]) showed a strong relationship with mitochondrial respiratory function and content in the type 1 diabetes cohort.
Conclusions/interpretation
In middle- to older-aged adults with uncomplicated type 1 diabetes, we conclude that skeletal muscle mitochondria differentially adapt to type 1 diabetes and demonstrate sexual dimorphism. Importantly, these cellular alterations were significantly associated with our metric of aerobic fitness (PWC
130
) and preceded notable impairments in skeletal mass and strength.
Graphical abstract</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-021-05540-1</identifier><identifier>PMID: 34392397</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Aerobic capacity ; Aged ; Biopsy ; Cardiorespiratory fitness ; Cell Respiration - physiology ; Citrate synthase ; Cristae ; Diabetes ; Diabetes mellitus (insulin dependent) ; Diabetes Mellitus, Type 1 - metabolism ; Electron microscopy ; Electron transport chain ; Electron Transport Complex I - metabolism ; Electron Transport Complex II - metabolism ; Endocrinology & Metabolism ; Female ; Human Physiology ; Humans ; Internal Medicine ; Life Sciences & Biomedicine ; Male ; Medicine ; Medicine & Public Health ; Mens health ; Metabolic Diseases ; Middle Aged ; Mitochondria ; Mitochondria, Muscle - metabolism ; Muscle, Skeletal - metabolism ; Musculoskeletal system ; Older people ; Oxidative Phosphorylation ; Oxygen Consumption - physiology ; Phosphorylation ; Physical activity ; Physical fitness ; Pyruvic acid ; Respiratory Mechanics ; Science & Technology ; Sexual dimorphism ; Skeletal muscle ; Women ; Womens health</subject><ispartof>Diabetologia, 2021-11, Vol.64 (11), p.2517-2533</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>11</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000684911200004</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c419t-5638ab05ba0d8d1c3aadb8c3c6bfa52b4572f079ee6ff3d36ff93058dc57ff773</citedby><cites>FETCH-LOGICAL-c419t-5638ab05ba0d8d1c3aadb8c3c6bfa52b4572f079ee6ff3d36ff93058dc57ff773</cites><orcidid>0000-0003-0312-3746 ; 0000-0003-2338-7714 ; 0000-0002-4732-5473 ; 0000-0002-5745-5888 ; 0000-0002-4592-4093 ; 0000-0003-4974-4820</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00125-021-05540-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00125-021-05540-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,39263,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34392397$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Monaco, Cynthia M. F.</creatorcontrib><creatorcontrib>Tarnopolsky, Mark A.</creatorcontrib><creatorcontrib>Dial, Athan G.</creatorcontrib><creatorcontrib>Nederveen, Joshua P.</creatorcontrib><creatorcontrib>Rebalka, Irena A.</creatorcontrib><creatorcontrib>Nguyen, Maria</creatorcontrib><creatorcontrib>Turner, Lauren V.</creatorcontrib><creatorcontrib>Perry, Christopher G. R.</creatorcontrib><creatorcontrib>Ljubicic, Vladimir</creatorcontrib><creatorcontrib>Hawke, Thomas J.</creatorcontrib><title>Normal to enhanced intrinsic mitochondrial respiration in skeletal muscle of middle- to older-aged women and men with uncomplicated type 1 diabetes</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>DIABETOLOGIA</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis
This study interrogated mitochondrial respiratory function and content in skeletal muscle biopsies of healthy adults between 30 and 72 years old with and without uncomplicated type 1 diabetes.
Methods
Participants (12 women/nine men) with type 1 diabetes (48 ± 11 years of age), without overt complications, were matched for age, sex, BMI and level of physical activity to participants without diabetes (control participants) (49 ± 12 years of age). Participants underwent a Bergström biopsy of the
vastus lateralis
to assess mitochondrial respiratory function using high-resolution respirometry and citrate synthase activity. Electron microscopy was used to quantify mitochondrial content and cristae (pixel) density.
Results
Mean mitochondrial area density was 27% lower (
p
= 0.006) in participants with type 1 diabetes compared with control participants. This was largely due to smaller mitochondrial fragments in women with type 1 diabetes (−18%,
p
= 0.057), as opposed to a decrease in the total number of mitochondrial fragments in men with diabetes (−28%,
p
= 0.130). Mitochondrial respiratory measures, whether estimated per milligram of tissue (i.e. mass-specific) or normalised to area density (i.e. intrinsic mitochondrial function), differed between cohorts, and demonstrated sexual dimorphism. Mass-specific mitochondrial oxidative phosphorylation (OXPHOS) capacity with the substrates for complex I and complex II (C
I + II
) was significantly lower (−24%,
p
= 0.033) in women with type 1 diabetes compared with control participants, whereas mass-specific OXPHOS capacities with substrates for complex I only (pyruvate [C
I pyr
] or glutamate [C
I glu
]) or complex II only (succinate [C
II succ
]) were not different (
p >
0.404). No statistical differences (
p
> 0.397) were found in mass-specific OXPHOS capacity in men with type 1 diabetes compared with control participants despite a 42% non-significant increase in C
I glu
OXPHOS capacity (
p
= 0.218). In contrast, intrinsic C
I + II
OXPHOS capacity was not different in women with type 1 diabetes (+5%,
p
= 0.378), whereas in men with type 1 diabetes it was 25% higher (
p
= 0.163) compared with control participants. Men with type 1 diabetes also demonstrated higher intrinsic OXPHOS capacity for C
I pyr
(+50%,
p
= 0.159), C
I glu
(+88%,
p
= 0.033) and C
II succ
(+28%,
p
= 0.123), as well as higher intrinsic respiratory rates with low (more physiological) concentrations of either ADP, pyruvate, glutamate or succinate (
p
< 0.012). Women with type 1 diabetes had higher (
p
< 0.003) intrinsic respiratory rates with low concentrations of succinate only. Calculated aerobic fitness (Physical Working Capacity Test [PWC
130
]) showed a strong relationship with mitochondrial respiratory function and content in the type 1 diabetes cohort.
Conclusions/interpretation
In middle- to older-aged adults with uncomplicated type 1 diabetes, we conclude that skeletal muscle mitochondria differentially adapt to type 1 diabetes and demonstrate sexual dimorphism. Importantly, these cellular alterations were significantly associated with our metric of aerobic fitness (PWC
130
) and preceded notable impairments in skeletal mass and strength.
Graphical abstract</description><subject>Adult</subject><subject>Aerobic capacity</subject><subject>Aged</subject><subject>Biopsy</subject><subject>Cardiorespiratory fitness</subject><subject>Cell Respiration - physiology</subject><subject>Citrate synthase</subject><subject>Cristae</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Diabetes Mellitus, Type 1 - metabolism</subject><subject>Electron microscopy</subject><subject>Electron transport chain</subject><subject>Electron Transport Complex I - metabolism</subject><subject>Electron Transport Complex II - metabolism</subject><subject>Endocrinology & Metabolism</subject><subject>Female</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Life Sciences & Biomedicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mens health</subject><subject>Metabolic Diseases</subject><subject>Middle Aged</subject><subject>Mitochondria</subject><subject>Mitochondria, Muscle - metabolism</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Musculoskeletal system</subject><subject>Older people</subject><subject>Oxidative Phosphorylation</subject><subject>Oxygen Consumption - physiology</subject><subject>Phosphorylation</subject><subject>Physical activity</subject><subject>Physical fitness</subject><subject>Pyruvic acid</subject><subject>Respiratory Mechanics</subject><subject>Science & Technology</subject><subject>Sexual dimorphism</subject><subject>Skeletal muscle</subject><subject>Women</subject><subject>Womens health</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkcuKFDEUhoMoTjv6Ai4k4EaQaK51WUrjDQbdKLgrUsnJdMaqpE1SNPMcvrCpqXEEF-ImCcn3_5zwIfSU0VeM0vZ1ppRxRShnhColKWH30I5JwQmVvLuPdus7YV3z7Qw9yvmKUiqUbB6iMyFFz0Xf7tDPTzHNesIlYggHHQxY7ENJPmRv8OxLNIcYbPKVSZCPPuniY6gMzt9hglLv5yWbCXB0lbd2ArK2xclCIvqy9p3iDAHrYPG6n3w54CWYOB8nb3SpQLk-AmbYej1CgfwYPXB6yvDkdj9HX9-9_bL_QC4-v_-4f3NBjGR9IaoRnR6pGjW1nWVGaG3HzgjTjE4rPkrVckfbHqBxTlhR115Q1VmjWufaVpyjF1vvMcUfC-QyzD4bmCYdIC554KphPeuElBV9_hd6FZcU6nSVanvZtC3tKsU3yqSYcwI3HJOfdboeGB1WZcOmbKjKhhtlA6uhZ7fVyziDvYv8dlSBlxtwgjG6bDxUS3dYldp0smeM1xNdJ-3-n977cqNzH5dQalRs0VzxcAnpzyf_Mf8vM23Etg</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Monaco, Cynthia M. F.</creator><creator>Tarnopolsky, Mark A.</creator><creator>Dial, Athan G.</creator><creator>Nederveen, Joshua P.</creator><creator>Rebalka, Irena A.</creator><creator>Nguyen, Maria</creator><creator>Turner, Lauren V.</creator><creator>Perry, Christopher G. R.</creator><creator>Ljubicic, Vladimir</creator><creator>Hawke, Thomas J.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature</general><general>Springer Nature B.V</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0312-3746</orcidid><orcidid>https://orcid.org/0000-0003-2338-7714</orcidid><orcidid>https://orcid.org/0000-0002-4732-5473</orcidid><orcidid>https://orcid.org/0000-0002-5745-5888</orcidid><orcidid>https://orcid.org/0000-0002-4592-4093</orcidid><orcidid>https://orcid.org/0000-0003-4974-4820</orcidid></search><sort><creationdate>20211101</creationdate><title>Normal to enhanced intrinsic mitochondrial respiration in skeletal muscle of middle- to older-aged women and men with uncomplicated type 1 diabetes</title><author>Monaco, Cynthia M. F. ; Tarnopolsky, Mark A. ; Dial, Athan G. ; Nederveen, Joshua P. ; Rebalka, Irena A. ; Nguyen, Maria ; Turner, Lauren V. ; Perry, Christopher G. R. ; Ljubicic, Vladimir ; Hawke, Thomas J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-5638ab05ba0d8d1c3aadb8c3c6bfa52b4572f079ee6ff3d36ff93058dc57ff773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Aerobic capacity</topic><topic>Aged</topic><topic>Biopsy</topic><topic>Cardiorespiratory fitness</topic><topic>Cell Respiration - physiology</topic><topic>Citrate synthase</topic><topic>Cristae</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Diabetes Mellitus, Type 1 - metabolism</topic><topic>Electron microscopy</topic><topic>Electron transport chain</topic><topic>Electron Transport Complex I - metabolism</topic><topic>Electron Transport Complex II - metabolism</topic><topic>Endocrinology & Metabolism</topic><topic>Female</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Life Sciences & Biomedicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mens health</topic><topic>Metabolic Diseases</topic><topic>Middle Aged</topic><topic>Mitochondria</topic><topic>Mitochondria, Muscle - metabolism</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Musculoskeletal system</topic><topic>Older people</topic><topic>Oxidative Phosphorylation</topic><topic>Oxygen Consumption - physiology</topic><topic>Phosphorylation</topic><topic>Physical activity</topic><topic>Physical fitness</topic><topic>Pyruvic acid</topic><topic>Respiratory Mechanics</topic><topic>Science & Technology</topic><topic>Sexual dimorphism</topic><topic>Skeletal muscle</topic><topic>Women</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Monaco, Cynthia M. F.</creatorcontrib><creatorcontrib>Tarnopolsky, Mark A.</creatorcontrib><creatorcontrib>Dial, Athan G.</creatorcontrib><creatorcontrib>Nederveen, Joshua P.</creatorcontrib><creatorcontrib>Rebalka, Irena A.</creatorcontrib><creatorcontrib>Nguyen, Maria</creatorcontrib><creatorcontrib>Turner, Lauren V.</creatorcontrib><creatorcontrib>Perry, Christopher G. R.</creatorcontrib><creatorcontrib>Ljubicic, Vladimir</creatorcontrib><creatorcontrib>Hawke, Thomas J.</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Monaco, Cynthia M. F.</au><au>Tarnopolsky, Mark A.</au><au>Dial, Athan G.</au><au>Nederveen, Joshua P.</au><au>Rebalka, Irena A.</au><au>Nguyen, Maria</au><au>Turner, Lauren V.</au><au>Perry, Christopher G. R.</au><au>Ljubicic, Vladimir</au><au>Hawke, Thomas J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Normal to enhanced intrinsic mitochondrial respiration in skeletal muscle of middle- to older-aged women and men with uncomplicated type 1 diabetes</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><stitle>DIABETOLOGIA</stitle><addtitle>Diabetologia</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>64</volume><issue>11</issue><spage>2517</spage><epage>2533</epage><pages>2517-2533</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis
This study interrogated mitochondrial respiratory function and content in skeletal muscle biopsies of healthy adults between 30 and 72 years old with and without uncomplicated type 1 diabetes.
Methods
Participants (12 women/nine men) with type 1 diabetes (48 ± 11 years of age), without overt complications, were matched for age, sex, BMI and level of physical activity to participants without diabetes (control participants) (49 ± 12 years of age). Participants underwent a Bergström biopsy of the
vastus lateralis
to assess mitochondrial respiratory function using high-resolution respirometry and citrate synthase activity. Electron microscopy was used to quantify mitochondrial content and cristae (pixel) density.
Results
Mean mitochondrial area density was 27% lower (
p
= 0.006) in participants with type 1 diabetes compared with control participants. This was largely due to smaller mitochondrial fragments in women with type 1 diabetes (−18%,
p
= 0.057), as opposed to a decrease in the total number of mitochondrial fragments in men with diabetes (−28%,
p
= 0.130). Mitochondrial respiratory measures, whether estimated per milligram of tissue (i.e. mass-specific) or normalised to area density (i.e. intrinsic mitochondrial function), differed between cohorts, and demonstrated sexual dimorphism. Mass-specific mitochondrial oxidative phosphorylation (OXPHOS) capacity with the substrates for complex I and complex II (C
I + II
) was significantly lower (−24%,
p
= 0.033) in women with type 1 diabetes compared with control participants, whereas mass-specific OXPHOS capacities with substrates for complex I only (pyruvate [C
I pyr
] or glutamate [C
I glu
]) or complex II only (succinate [C
II succ
]) were not different (
p >
0.404). No statistical differences (
p
> 0.397) were found in mass-specific OXPHOS capacity in men with type 1 diabetes compared with control participants despite a 42% non-significant increase in C
I glu
OXPHOS capacity (
p
= 0.218). In contrast, intrinsic C
I + II
OXPHOS capacity was not different in women with type 1 diabetes (+5%,
p
= 0.378), whereas in men with type 1 diabetes it was 25% higher (
p
= 0.163) compared with control participants. Men with type 1 diabetes also demonstrated higher intrinsic OXPHOS capacity for C
I pyr
(+50%,
p
= 0.159), C
I glu
(+88%,
p
= 0.033) and C
II succ
(+28%,
p
= 0.123), as well as higher intrinsic respiratory rates with low (more physiological) concentrations of either ADP, pyruvate, glutamate or succinate (
p
< 0.012). Women with type 1 diabetes had higher (
p
< 0.003) intrinsic respiratory rates with low concentrations of succinate only. Calculated aerobic fitness (Physical Working Capacity Test [PWC
130
]) showed a strong relationship with mitochondrial respiratory function and content in the type 1 diabetes cohort.
Conclusions/interpretation
In middle- to older-aged adults with uncomplicated type 1 diabetes, we conclude that skeletal muscle mitochondria differentially adapt to type 1 diabetes and demonstrate sexual dimorphism. Importantly, these cellular alterations were significantly associated with our metric of aerobic fitness (PWC
130
) and preceded notable impairments in skeletal mass and strength.
Graphical abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34392397</pmid><doi>10.1007/s00125-021-05540-1</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0003-0312-3746</orcidid><orcidid>https://orcid.org/0000-0003-2338-7714</orcidid><orcidid>https://orcid.org/0000-0002-4732-5473</orcidid><orcidid>https://orcid.org/0000-0002-5745-5888</orcidid><orcidid>https://orcid.org/0000-0002-4592-4093</orcidid><orcidid>https://orcid.org/0000-0003-4974-4820</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-186X |
| ispartof | Diabetologia, 2021-11, Vol.64 (11), p.2517-2533 |
| issn | 0012-186X 1432-0428 |
| language | eng |
| recordid | cdi_pubmed_primary_34392397 |
| source | MEDLINE; SpringerNature Journals; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /> |
| subjects | Adult Aerobic capacity Aged Biopsy Cardiorespiratory fitness Cell Respiration - physiology Citrate synthase Cristae Diabetes Diabetes mellitus (insulin dependent) Diabetes Mellitus, Type 1 - metabolism Electron microscopy Electron transport chain Electron Transport Complex I - metabolism Electron Transport Complex II - metabolism Endocrinology & Metabolism Female Human Physiology Humans Internal Medicine Life Sciences & Biomedicine Male Medicine Medicine & Public Health Mens health Metabolic Diseases Middle Aged Mitochondria Mitochondria, Muscle - metabolism Muscle, Skeletal - metabolism Musculoskeletal system Older people Oxidative Phosphorylation Oxygen Consumption - physiology Phosphorylation Physical activity Physical fitness Pyruvic acid Respiratory Mechanics Science & Technology Sexual dimorphism Skeletal muscle Women Womens health |
| title | Normal to enhanced intrinsic mitochondrial respiration in skeletal muscle of middle- to older-aged women and men with uncomplicated type 1 diabetes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-13T21%3A44%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Normal%20to%20enhanced%20intrinsic%20mitochondrial%20respiration%20in%20skeletal%20muscle%20of%20middle-%20to%20older-aged%20women%20and%20men%20with%20uncomplicated%20type%201%20diabetes&rft.jtitle=Diabetologia&rft.au=Monaco,%20Cynthia%20M.%20F.&rft.date=2021-11-01&rft.volume=64&rft.issue=11&rft.spage=2517&rft.epage=2533&rft.pages=2517-2533&rft.issn=0012-186X&rft.eissn=1432-0428&rft_id=info:doi/10.1007/s00125-021-05540-1&rft_dat=%3Cproquest_pubme%3E2561918344%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2579467708&rft_id=info:pmid/34392397&rfr_iscdi=true |