Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts
Artikel i vetenskaplig tidskrift, 2022
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.
Författare
A. S. Meijnikman
Spaarne Gasthuis
Universiteit Van Amsterdam
C. C. Van Olden
Universiteit Van Amsterdam
O. Aydin
Spaarne Gasthuis
Universiteit Van Amsterdam
H. Herrema
Universiteit Van Amsterdam
Dorota Kaminska
Itä-Suomen Yliopisto
Dimitra Lappa
Chalmers, Biologi och bioteknik, Systembiologi
Ville Männistö
Kuopio University Hospital
Valentina Tremaroli
Wallenberg Lab.
L. E. Olofsson
Wallenberg Lab.
Maurits de Brauw
Spaarne Gasthuis
A. W. Van de Laar
Spaarne Gasthuis
J. Verheij
Universiteit Van Amsterdam
V. E.A. Gerdes
Spaarne Gasthuis
Universiteit Van Amsterdam
Thue W. Schwartz
Köpenhamns universitet
Jens B Nielsen
Chalmers, Biologi och bioteknik, Systembiologi
Fredrik Bäckhed
Köpenhamns universitet
Sahlgrenska universitetssjukhuset
Wallenberg Lab.
Päivi Pajukanta
University of California at Los Angeles
Jussi Pihlajamäki
Kuopio University Hospital
Itä-Suomen Yliopisto
Tamar Tchkonia
Mayo Clinic
James L. Kirkland
Mayo Clinic
Folkert Kuipers
Rijksuniversiteit Groningen
M. Nieuwdorp
Universiteit Van Amsterdam
A. K. Groen
Universiteit Van Amsterdam
Rijksuniversiteit Groningen
Diabetes
00121797 (ISSN) 1939327X (eISSN)
Vol. 71 9 1929-1936Ämneskategorier
Endokrinologi och diabetes
Gastroenterologi
Näringslära
DOI
10.2337/db21-1076
PubMed
35713877