Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts

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Standard

Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts. / Meijnikman, Abraham S.; van Olden, Casper C.; Aydin, Ömrüm; Herrema, Hilde; Kaminska, Dorota; Lappa, Dimitra; Männistö, Ville; Tremaroli, Valentina; Olofsson, Louise E.; de Brauw, Maurits; van de Laar, Arnold; Verheij, Joanne; Gerdes, Victor E.A.; Schwartz, Thue W.; Nielsen, Jens; Bäckhed, Fredrik; Pajukanta, Päivi; Pihlajamäki, Jussi; Tchkonia, Tamar; Kirkland, James L.; Kuipers, Folkert; Nieuwdorp, Max; Groen, Albert K.

In: Diabetes, Vol. 71, No. 9, 2022, p. 1929-1936.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Meijnikman, AS, van Olden, CC, Aydin, Ö, Herrema, H, Kaminska, D, Lappa, D, Männistö, V, Tremaroli, V, Olofsson, LE, de Brauw, M, van de Laar, A, Verheij, J, Gerdes, VEA, Schwartz, TW, Nielsen, J, Bäckhed, F, Pajukanta, P, Pihlajamäki, J, Tchkonia, T, Kirkland, JL, Kuipers, F, Nieuwdorp, M & Groen, AK 2022, 'Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts', Diabetes, vol. 71, no. 9, pp. 1929-1936. https://doi.org/10.2337/db21-1076

APA

Meijnikman, A. S., van Olden, C. C., Aydin, Ö., Herrema, H., Kaminska, D., Lappa, D., Männistö, V., Tremaroli, V., Olofsson, L. E., de Brauw, M., van de Laar, A., Verheij, J., Gerdes, V. E. A., Schwartz, T. W., Nielsen, J., Bäckhed, F., Pajukanta, P., Pihlajamäki, J., Tchkonia, T., ... Groen, A. K. (2022). Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts. Diabetes, 71(9), 1929-1936. https://doi.org/10.2337/db21-1076

Vancouver

Meijnikman AS, van Olden CC, Aydin Ö, Herrema H, Kaminska D, Lappa D et al. Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts. Diabetes. 2022;71(9):1929-1936. https://doi.org/10.2337/db21-1076

Author

Meijnikman, Abraham S. ; van Olden, Casper C. ; Aydin, Ömrüm ; Herrema, Hilde ; Kaminska, Dorota ; Lappa, Dimitra ; Männistö, Ville ; Tremaroli, Valentina ; Olofsson, Louise E. ; de Brauw, Maurits ; van de Laar, Arnold ; Verheij, Joanne ; Gerdes, Victor E.A. ; Schwartz, Thue W. ; Nielsen, Jens ; Bäckhed, Fredrik ; Pajukanta, Päivi ; Pihlajamäki, Jussi ; Tchkonia, Tamar ; Kirkland, James L. ; Kuipers, Folkert ; Nieuwdorp, Max ; Groen, Albert K. / Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts. In: Diabetes. 2022 ; Vol. 71, No. 9. pp. 1929-1936.

Bibtex

@article{b2b2602af9c04bfd89c381a0982e59a5,
title = "Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts",
abstract = "Cellular senescence is an essentially irreversible growth arrest that occurs in response to various cellular stressors and may contribute to development of type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD). In this article, we investigated whether chronically elevated insulin levels are associated with cellular senescence in the human liver. In 107 individuals undergoing bariatric surgery, hepatic senescence markers were assessed by immunohistochemistry as well as transcriptomics. A subset of 180 participants from the ongoing Finnish Kuopio OBesity Surgery (KOBS) study was used as validation cohort. We found plasma insulin to be highly associated with various markers of cellular senescence in liver tissue. The liver transcriptome of individuals with high insulin revealed significant upregulation of several genes associated with senescence: p21, TGFβ, PI3K, HLA-G, IL8, p38, Ras, and E2F. Insulin associated with hepatic senescence independently of NAFLD and plasma glucose. By using transcriptomic data from the KOBS study, we could validate the association of insulin with p21 in the liver. Our results support a potential role for hyperinsulinemia in induction of cellular senescence in the liver. These findings suggest possible benefits of lowering insulin levels in obese individuals with insulin resistance.",
author = "Meijnikman, {Abraham S.} and {van Olden}, {Casper C.} and {\"O}mr{\"u}m Aydin and Hilde Herrema and Dorota Kaminska and Dimitra Lappa and Ville M{\"a}nnist{\"o} and Valentina Tremaroli and Olofsson, {Louise E.} and {de Brauw}, Maurits and {van de Laar}, Arnold and Joanne Verheij and Gerdes, {Victor E.A.} and Schwartz, {Thue W.} and Jens Nielsen and Fredrik B{\"a}ckhed and P{\"a}ivi Pajukanta and Jussi Pihlajam{\"a}ki and Tamar Tchkonia and Kirkland, {James L.} and Folkert Kuipers and Max Nieuwdorp and Groen, {Albert K.}",
note = "Publisher Copyright: {\textcopyright} 2022 by the American Diabetes Association.",
year = "2022",
doi = "10.2337/db21-1076",
language = "English",
volume = "71",
pages = "1929--1936",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "9",

}

RIS

TY - JOUR

T1 - Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts

AU - Meijnikman, Abraham S.

AU - van Olden, Casper C.

AU - Aydin, Ömrüm

AU - Herrema, Hilde

AU - Kaminska, Dorota

AU - Lappa, Dimitra

AU - Männistö, Ville

AU - Tremaroli, Valentina

AU - Olofsson, Louise E.

AU - de Brauw, Maurits

AU - van de Laar, Arnold

AU - Verheij, Joanne

AU - Gerdes, Victor E.A.

AU - Schwartz, Thue W.

AU - Nielsen, Jens

AU - Bäckhed, Fredrik

AU - Pajukanta, Päivi

AU - Pihlajamäki, Jussi

AU - Tchkonia, Tamar

AU - Kirkland, James L.

AU - Kuipers, Folkert

AU - Nieuwdorp, Max

AU - Groen, Albert K.

N1 - Publisher Copyright: © 2022 by the American Diabetes Association.

PY - 2022

Y1 - 2022

N2 - Cellular senescence is an essentially irreversible growth arrest that occurs in response to various cellular stressors and may contribute to development of type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD). In this article, we investigated whether chronically elevated insulin levels are associated with cellular senescence in the human liver. In 107 individuals undergoing bariatric surgery, hepatic senescence markers were assessed by immunohistochemistry as well as transcriptomics. A subset of 180 participants from the ongoing Finnish Kuopio OBesity Surgery (KOBS) study was used as validation cohort. We found plasma insulin to be highly associated with various markers of cellular senescence in liver tissue. The liver transcriptome of individuals with high insulin revealed significant upregulation of several genes associated with senescence: p21, TGFβ, PI3K, HLA-G, IL8, p38, Ras, and E2F. Insulin associated with hepatic senescence independently of NAFLD and plasma glucose. By using transcriptomic data from the KOBS study, we could validate the association of insulin with p21 in the liver. Our results support a potential role for hyperinsulinemia in induction of cellular senescence in the liver. These findings suggest possible benefits of lowering insulin levels in obese individuals with insulin resistance.

AB - Cellular senescence is an essentially irreversible growth arrest that occurs in response to various cellular stressors and may contribute to development of type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD). In this article, we investigated whether chronically elevated insulin levels are associated with cellular senescence in the human liver. In 107 individuals undergoing bariatric surgery, hepatic senescence markers were assessed by immunohistochemistry as well as transcriptomics. A subset of 180 participants from the ongoing Finnish Kuopio OBesity Surgery (KOBS) study was used as validation cohort. We found plasma insulin to be highly associated with various markers of cellular senescence in liver tissue. The liver transcriptome of individuals with high insulin revealed significant upregulation of several genes associated with senescence: p21, TGFβ, PI3K, HLA-G, IL8, p38, Ras, and E2F. Insulin associated with hepatic senescence independently of NAFLD and plasma glucose. By using transcriptomic data from the KOBS study, we could validate the association of insulin with p21 in the liver. Our results support a potential role for hyperinsulinemia in induction of cellular senescence in the liver. These findings suggest possible benefits of lowering insulin levels in obese individuals with insulin resistance.

U2 - 10.2337/db21-1076

DO - 10.2337/db21-1076

M3 - Journal article

C2 - 35713877

AN - SCOPUS:85137008651

VL - 71

SP - 1929

EP - 1936

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 9

ER -

ID: 318920731