The relationship of mitochondrial dysfunction and the development of insulin resistance in Cushing’s syndrome
Jana Ježková,1 Viktória Ďurovcová,1 Laszlo Wenchich,2,3 Hana Hansíková,3 Jiří Zeman,3 Václav Hána,1 Josef Marek,1 Zdeňka Lacinová,4,5 Martin Haluzík,4,5 Michal Kršek11Third Depart...
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Dove Medical Press
2019
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oai:doaj.org-article:00dc79d3755540daa799cd6cc1f7685f2021-12-02T03:19:59ZThe relationship of mitochondrial dysfunction and the development of insulin resistance in Cushing’s syndrome1178-7007https://doaj.org/article/00dc79d3755540daa799cd6cc1f7685f2019-08-01T00:00:00Zhttps://www.dovepress.com/the-relationship-of-mitochondrial-dysfunction-and-the-development-of-i-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Jana Ježková,1 Viktória Ďurovcová,1 Laszlo Wenchich,2,3 Hana Hansíková,3 Jiří Zeman,3 Václav Hána,1 Josef Marek,1 Zdeňka Lacinová,4,5 Martin Haluzík,4,5 Michal Kršek11Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 2Institute of Rheumatology, Prague, Czech Republic; 3Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 4Institute of Medical Biochemistry and Laboratory Diagnostic, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 5Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech RepublicCorrespondence: Jana JežkováThird Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 1128 02 Praha 2, Prague, Czech RepublicTel +420 60 641 2613Fax +420 22 491 9780Email fjjezek@cmail.czPurpose: Cushing’s syndrome is characterized by metabolic disturbances including insulin resistance. Mitochondrial dysfunction is one pathogenic factor in the development of insulin resistance in patients with obesity. We explored whether mitochondrial dysfunction correlates with insulin resistance and other metabolic complications.Patients and methods: We investigated the changes of mRNA expression of genes encoding selected subunits of oxidative phosphorylation system (OXPHOS), pyruvate dehydrogenase (PDH) and citrate synthase (CS) in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) and mitochondrial enzyme activity in platelets of 24 patients with active Cushing’s syndrome and in 9 of them after successful treatment and 22 healthy control subjects.Results: Patients with active Cushing’s syndrome had significantly increased body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and serum lipids relative to the control group. The expression of all investigated genes for selected mitochondrial proteins was decreased in SCAT in patients with active Cushing’s syndrome and remained decreased after successful treatment. The expression of most tested genes in SCAT correlated inversely with BMI and HOMA-IR. The expression of genes encoding selected OXPHOS subunits and CS was increased in PM in patients with active Cushing’s syndrome with a tendency to decrease toward normal levels after cure. Patients with active Cushing’s syndrome showed increased enzyme activity of complex I (NQR) in platelets.Conclusion: Mitochondrial function in SCAT in patients with Cushing’s syndrome is impaired and only slightly affected by its treatment which may reflect ongoing metabolic disturbances even after successful treatment of Cushing’s syndrome.Keywords: Cushing’s syndrome, insulin resistance, mitochondrial enzyme activity, gene expressionJežková JĎurovcová VWenchich LHansíková HZeman JHána VMarek JLacinová ZHaluzík MKršek MDove Medical PressarticleCushing’s syndromeinsulin resistancemitochondrial enzyme activitygene expressionSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 12, Pp 1459-1471 (2019) |
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Cushing’s syndrome insulin resistance mitochondrial enzyme activity gene expression Specialties of internal medicine RC581-951 |
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Cushing’s syndrome insulin resistance mitochondrial enzyme activity gene expression Specialties of internal medicine RC581-951 Ježková J Ďurovcová V Wenchich L Hansíková H Zeman J Hána V Marek J Lacinová Z Haluzík M Kršek M The relationship of mitochondrial dysfunction and the development of insulin resistance in Cushing’s syndrome |
| description |
Jana Ježková,1 Viktória Ďurovcová,1 Laszlo Wenchich,2,3 Hana Hansíková,3 Jiří Zeman,3 Václav Hána,1 Josef Marek,1 Zdeňka Lacinová,4,5 Martin Haluzík,4,5 Michal Kršek11Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 2Institute of Rheumatology, Prague, Czech Republic; 3Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 4Institute of Medical Biochemistry and Laboratory Diagnostic, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 5Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech RepublicCorrespondence: Jana JežkováThird Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 1128 02 Praha 2, Prague, Czech RepublicTel +420 60 641 2613Fax +420 22 491 9780Email fjjezek@cmail.czPurpose: Cushing’s syndrome is characterized by metabolic disturbances including insulin resistance. Mitochondrial dysfunction is one pathogenic factor in the development of insulin resistance in patients with obesity. We explored whether mitochondrial dysfunction correlates with insulin resistance and other metabolic complications.Patients and methods: We investigated the changes of mRNA expression of genes encoding selected subunits of oxidative phosphorylation system (OXPHOS), pyruvate dehydrogenase (PDH) and citrate synthase (CS) in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) and mitochondrial enzyme activity in platelets of 24 patients with active Cushing’s syndrome and in 9 of them after successful treatment and 22 healthy control subjects.Results: Patients with active Cushing’s syndrome had significantly increased body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and serum lipids relative to the control group. The expression of all investigated genes for selected mitochondrial proteins was decreased in SCAT in patients with active Cushing’s syndrome and remained decreased after successful treatment. The expression of most tested genes in SCAT correlated inversely with BMI and HOMA-IR. The expression of genes encoding selected OXPHOS subunits and CS was increased in PM in patients with active Cushing’s syndrome with a tendency to decrease toward normal levels after cure. Patients with active Cushing’s syndrome showed increased enzyme activity of complex I (NQR) in platelets.Conclusion: Mitochondrial function in SCAT in patients with Cushing’s syndrome is impaired and only slightly affected by its treatment which may reflect ongoing metabolic disturbances even after successful treatment of Cushing’s syndrome.Keywords: Cushing’s syndrome, insulin resistance, mitochondrial enzyme activity, gene expression |
| format |
article |
| author |
Ježková J Ďurovcová V Wenchich L Hansíková H Zeman J Hána V Marek J Lacinová Z Haluzík M Kršek M |
| author_facet |
Ježková J Ďurovcová V Wenchich L Hansíková H Zeman J Hána V Marek J Lacinová Z Haluzík M Kršek M |
| author_sort |
Ježková J |
| title |
The relationship of mitochondrial dysfunction and the development of insulin resistance in Cushing’s syndrome |
| title_short |
The relationship of mitochondrial dysfunction and the development of insulin resistance in Cushing’s syndrome |
| title_full |
The relationship of mitochondrial dysfunction and the development of insulin resistance in Cushing’s syndrome |
| title_fullStr |
The relationship of mitochondrial dysfunction and the development of insulin resistance in Cushing’s syndrome |
| title_full_unstemmed |
The relationship of mitochondrial dysfunction and the development of insulin resistance in Cushing’s syndrome |
| title_sort |
relationship of mitochondrial dysfunction and the development of insulin resistance in cushing’s syndrome |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/00dc79d3755540daa799cd6cc1f7685f |
| work_keys_str_mv |
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