Circulating Monocyte and Lymphocyte Populations in Healthy First-Degree Relatives of Type 2 Diabetic Patients at Fasting and during Short-Term Hyperinsulinemia
Aim. The development of type 2 diabetes (T2DM) is associated with disturbances of immune status that may be reflected by alterations of the profile of circulating immune cells. In order to study whether there exists genetic predisposition to these alterations, we investigated the relative content of...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/1491083 |
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| author | Michaela Šiklová Eva Krauzová Barbora Svobodová Jana Kračmerová Marek Štěpán Michal Koc Vladimír Štich Lenka Rossmeislová |
| author_facet | Michaela Šiklová Eva Krauzová Barbora Svobodová Jana Kračmerová Marek Štěpán Michal Koc Vladimír Štich Lenka Rossmeislová |
| author_sort | Michaela Šiklová |
| collection | DOAJ |
| description | Aim. The development of type 2 diabetes (T2DM) is associated with disturbances of immune status that may be reflected by alterations of the profile of circulating immune cells. In order to study whether there exists genetic predisposition to these alterations, we investigated the relative content of circulating monocyte and lymphocyte subpopulations at fasting condition and upon stimulation by short-term hyperinsulinemia in nondiabetic first-degree relatives (FDR) of T2DM patients and in control subjects. Materials and Methods. 19 nondiabetic (FDR) and 19 control subjects without a family history of diabetes (all men) matched for age and BMI underwent 2-hour hyperinsulinemic-euglycemic clamp. Blood samples taken before and at the end of the clamp were used for the flow cytometry analysis of lymphocyte and monocyte populations and for the assessment of cytokine levels. Results. At fasting conditions, FDR showed a higher CD4/CD8 ratio of peripheral lymphocytes, a higher percentage of Th17 lymphocytes, and a lower content of intermediate monocytes when compared to controls. The CD4/CD8 ratio correlated with fat mass, insulin, and HOMA-IR in the entire group of subjects. Hyperinsulinemia decreased a relative content of peripheral CD4+ and increased a relative content of CD8+ T lymphocytes, thus decreasing the CD4/CD8 ratio by 18-22% in both groups of subjects. In FDR but not in controls, the decrease of CD4+ T lymphocyte content was partially based on the decrease of TH2 and TH17 lymphocyte subpopulations. In control subjects but not in FDR, the number of intermediate monocytes has declined in response to hyperinsulinemia. Conclusion. The alterations of the CD4/CD8 lymphocyte ratio, relative content of TH17 cells, and intermediate monocytes in FDR are features of genetic predisposition to T2DM and may play a role in pathogenesis of T2DM. Short-term hyperinsulinemia affected mostly the immune cell populations deregulated in FDR subjects, which suggests important interplay between immune system homeostasis and insulin levels. |
| format | Article |
| id | doaj-art-a5a2dd28d96c463cbfa89f8b82531f8b |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-a5a2dd28d96c463cbfa89f8b82531f8b2025-02-03T01:21:21ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/14910831491083Circulating Monocyte and Lymphocyte Populations in Healthy First-Degree Relatives of Type 2 Diabetic Patients at Fasting and during Short-Term HyperinsulinemiaMichaela Šiklová0Eva Krauzová1Barbora Svobodová2Jana Kračmerová3Marek Štěpán4Michal Koc5Vladimír Štich6Lenka Rossmeislová7Department of Pathophysiology, Third Faculty of Medicine, Charles University, Prague 100 00, Czech RepublicDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague 100 00, Czech RepublicDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague 100 00, Czech RepublicDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague 100 00, Czech RepublicDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague 100 00, Czech RepublicDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague 100 00, Czech RepublicDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague 100 00, Czech RepublicDepartment of Pathophysiology, Third Faculty of Medicine, Charles University, Prague 100 00, Czech RepublicAim. The development of type 2 diabetes (T2DM) is associated with disturbances of immune status that may be reflected by alterations of the profile of circulating immune cells. In order to study whether there exists genetic predisposition to these alterations, we investigated the relative content of circulating monocyte and lymphocyte subpopulations at fasting condition and upon stimulation by short-term hyperinsulinemia in nondiabetic first-degree relatives (FDR) of T2DM patients and in control subjects. Materials and Methods. 19 nondiabetic (FDR) and 19 control subjects without a family history of diabetes (all men) matched for age and BMI underwent 2-hour hyperinsulinemic-euglycemic clamp. Blood samples taken before and at the end of the clamp were used for the flow cytometry analysis of lymphocyte and monocyte populations and for the assessment of cytokine levels. Results. At fasting conditions, FDR showed a higher CD4/CD8 ratio of peripheral lymphocytes, a higher percentage of Th17 lymphocytes, and a lower content of intermediate monocytes when compared to controls. The CD4/CD8 ratio correlated with fat mass, insulin, and HOMA-IR in the entire group of subjects. Hyperinsulinemia decreased a relative content of peripheral CD4+ and increased a relative content of CD8+ T lymphocytes, thus decreasing the CD4/CD8 ratio by 18-22% in both groups of subjects. In FDR but not in controls, the decrease of CD4+ T lymphocyte content was partially based on the decrease of TH2 and TH17 lymphocyte subpopulations. In control subjects but not in FDR, the number of intermediate monocytes has declined in response to hyperinsulinemia. Conclusion. The alterations of the CD4/CD8 lymphocyte ratio, relative content of TH17 cells, and intermediate monocytes in FDR are features of genetic predisposition to T2DM and may play a role in pathogenesis of T2DM. Short-term hyperinsulinemia affected mostly the immune cell populations deregulated in FDR subjects, which suggests important interplay between immune system homeostasis and insulin levels.http://dx.doi.org/10.1155/2019/1491083 |
| spellingShingle | Michaela Šiklová Eva Krauzová Barbora Svobodová Jana Kračmerová Marek Štěpán Michal Koc Vladimír Štich Lenka Rossmeislová Circulating Monocyte and Lymphocyte Populations in Healthy First-Degree Relatives of Type 2 Diabetic Patients at Fasting and during Short-Term Hyperinsulinemia Mediators of Inflammation |
| title | Circulating Monocyte and Lymphocyte Populations in Healthy First-Degree Relatives of Type 2 Diabetic Patients at Fasting and during Short-Term Hyperinsulinemia |
| title_full | Circulating Monocyte and Lymphocyte Populations in Healthy First-Degree Relatives of Type 2 Diabetic Patients at Fasting and during Short-Term Hyperinsulinemia |
| title_fullStr | Circulating Monocyte and Lymphocyte Populations in Healthy First-Degree Relatives of Type 2 Diabetic Patients at Fasting and during Short-Term Hyperinsulinemia |
| title_full_unstemmed | Circulating Monocyte and Lymphocyte Populations in Healthy First-Degree Relatives of Type 2 Diabetic Patients at Fasting and during Short-Term Hyperinsulinemia |
| title_short | Circulating Monocyte and Lymphocyte Populations in Healthy First-Degree Relatives of Type 2 Diabetic Patients at Fasting and during Short-Term Hyperinsulinemia |
| title_sort | circulating monocyte and lymphocyte populations in healthy first degree relatives of type 2 diabetic patients at fasting and during short term hyperinsulinemia |
| url | http://dx.doi.org/10.1155/2019/1491083 |
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