Sex-specific alterations in creatine metabolism in cellular compartments of peripheral blood leukocytes in type 1 diabetes

The creatine (Cr)/creatine kinase (CK) system plays a crucial role in cellular energy metabolism, glucose control, and the immune response. This study aimed to investigate this system in the peripheral blood leukocytes (PBL) of Armenians with type 1 diabetes (T1D) who received insulin therapy. A tot...

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Main Authors: Nina Alchujyan, Elena Aghajanova, Nina Movsesyan, Arthur Melkonyan, Artashes Guevorkian, Armen Andreasyan, Margarita Hovhannisyan
Format: Article
Language:English
Published: AIMS Press 2024-12-01
Series:AIMS Bioengineering
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Online Access:https://www.aimspress.com/article/doi/10.3934/bioeng.2024028
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author Nina Alchujyan
Elena Aghajanova
Nina Movsesyan
Arthur Melkonyan
Artashes Guevorkian
Armen Andreasyan
Margarita Hovhannisyan
author_facet Nina Alchujyan
Elena Aghajanova
Nina Movsesyan
Arthur Melkonyan
Artashes Guevorkian
Armen Andreasyan
Margarita Hovhannisyan
author_sort Nina Alchujyan
collection DOAJ
description The creatine (Cr)/creatine kinase (CK) system plays a crucial role in cellular energy metabolism, glucose control, and the immune response. This study aimed to investigate this system in the peripheral blood leukocytes (PBL) of Armenians with type 1 diabetes (T1D) who received insulin therapy. A total of 270 Armenian participants were enrolled in the study and were divided into two age groups: Group I - included children and preadolescents; and Group II - included adolescents and young adults. Within each group, the participants were further categorized based on sex and disease duration: Recent-onset T1D (RO-T1D), and Long-term T1D (LT-T1D). A group of healthy individuals that were matched for age and sex served as controls. The glycemic control (GC) was assessed using the glycated hemoglobin (HbA1c) test. In girls of Group I with LT-T1D, both the Cr levels and CK activity were significantly reduced in both the cytoplasm and mitochondria of the PBL, despite having a good GC. In contrast, age-matched boys showed a relatively stable Cr metabolism. Beginning at puberty, only girls with LT-T1D and a poor GC showed decreased Cr levels and a reduced CK activity, which was most pronounced in the mitochondria. In boys of Group II, the cytoplasmic Cr levels decreased by half, regardless of the GC or disease duration, while the mitochondrial Cr levels decreased by 55% only in boys with LT-T1D and a poor GC. Their CK activity decreased by 80% in both cellular compartments, regardless of the GC and duration of diabetes. Notably, changes in the plasma were less specific. Our findings indicate age- and sex-dependent changes in Cr metabolism in the cytoplasm and mitochondria of PBL in Armenians with T1D, which are influenced by the glycemic status and the disease duration. Further extensive studies in this area may provide insights into potential strategies to control metabolism in T1D to counteract autoimmunity and immune dysregulation, and may also serve as a basis for the development of targeted therapeutic interventions.
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spelling doaj-art-f8659a9f31ca435d9033700ddc4d37422025-01-24T01:27:36ZengAIMS PressAIMS Bioengineering2375-14952024-12-0111460061610.3934/bioeng.2024028Sex-specific alterations in creatine metabolism in cellular compartments of peripheral blood leukocytes in type 1 diabetesNina Alchujyan0Elena Aghajanova1Nina Movsesyan2Arthur Melkonyan3Artashes Guevorkian4Armen Andreasyan5Margarita Hovhannisyan6Department of Bioengineering and Biocatalysis, Institute of Biochemistry named after H. Buniatyan, NAS RA, Yerevan-0014, Republic of ArmeniaDepartment of Endocrinology, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan-0025, Republic of ArmeniaDepartment of Bioengineering and Biocatalysis, Institute of Biochemistry named after H. Buniatyan, NAS RA, Yerevan-0014, Republic of ArmeniaDepartment of Endocrinology, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan-0025, Republic of ArmeniaDepartment of Endocrinology, Yerevan State Medical University named after Mkhitar Heratsi, Yerevan-0025, Republic of ArmeniaDepartment of Bioengineering and Biocatalysis, Institute of Biochemistry named after H. Buniatyan, NAS RA, Yerevan-0014, Republic of ArmeniaDepartment of Bioengineering and Biocatalysis, Institute of Biochemistry named after H. Buniatyan, NAS RA, Yerevan-0014, Republic of ArmeniaThe creatine (Cr)/creatine kinase (CK) system plays a crucial role in cellular energy metabolism, glucose control, and the immune response. This study aimed to investigate this system in the peripheral blood leukocytes (PBL) of Armenians with type 1 diabetes (T1D) who received insulin therapy. A total of 270 Armenian participants were enrolled in the study and were divided into two age groups: Group I - included children and preadolescents; and Group II - included adolescents and young adults. Within each group, the participants were further categorized based on sex and disease duration: Recent-onset T1D (RO-T1D), and Long-term T1D (LT-T1D). A group of healthy individuals that were matched for age and sex served as controls. The glycemic control (GC) was assessed using the glycated hemoglobin (HbA1c) test. In girls of Group I with LT-T1D, both the Cr levels and CK activity were significantly reduced in both the cytoplasm and mitochondria of the PBL, despite having a good GC. In contrast, age-matched boys showed a relatively stable Cr metabolism. Beginning at puberty, only girls with LT-T1D and a poor GC showed decreased Cr levels and a reduced CK activity, which was most pronounced in the mitochondria. In boys of Group II, the cytoplasmic Cr levels decreased by half, regardless of the GC or disease duration, while the mitochondrial Cr levels decreased by 55% only in boys with LT-T1D and a poor GC. Their CK activity decreased by 80% in both cellular compartments, regardless of the GC and duration of diabetes. Notably, changes in the plasma were less specific. Our findings indicate age- and sex-dependent changes in Cr metabolism in the cytoplasm and mitochondria of PBL in Armenians with T1D, which are influenced by the glycemic status and the disease duration. Further extensive studies in this area may provide insights into potential strategies to control metabolism in T1D to counteract autoimmunity and immune dysregulation, and may also serve as a basis for the development of targeted therapeutic interventions.https://www.aimspress.com/article/doi/10.3934/bioeng.2024028creatinecreatine kinasecytoplasmleukocytemitochondriatype 1 diabetes
spellingShingle Nina Alchujyan
Elena Aghajanova
Nina Movsesyan
Arthur Melkonyan
Artashes Guevorkian
Armen Andreasyan
Margarita Hovhannisyan
Sex-specific alterations in creatine metabolism in cellular compartments of peripheral blood leukocytes in type 1 diabetes
AIMS Bioengineering
creatine
creatine kinase
cytoplasm
leukocyte
mitochondria
type 1 diabetes
title Sex-specific alterations in creatine metabolism in cellular compartments of peripheral blood leukocytes in type 1 diabetes
title_full Sex-specific alterations in creatine metabolism in cellular compartments of peripheral blood leukocytes in type 1 diabetes
title_fullStr Sex-specific alterations in creatine metabolism in cellular compartments of peripheral blood leukocytes in type 1 diabetes
title_full_unstemmed Sex-specific alterations in creatine metabolism in cellular compartments of peripheral blood leukocytes in type 1 diabetes
title_short Sex-specific alterations in creatine metabolism in cellular compartments of peripheral blood leukocytes in type 1 diabetes
title_sort sex specific alterations in creatine metabolism in cellular compartments of peripheral blood leukocytes in type 1 diabetes
topic creatine
creatine kinase
cytoplasm
leukocyte
mitochondria
type 1 diabetes
url https://www.aimspress.com/article/doi/10.3934/bioeng.2024028
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