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Salt-inducible kinases are required for glucose uptake and insulin signaling in human adipocytes

Säll, Johanna LU orcid ; Lindahl, Maria LU ; Fritzen, Andreas M ; Fryklund, Claes LU ; Kopietz, Franziska LU orcid ; Nyberg, Emma LU ; Warvsten, Anna ; Morén, Björn LU orcid ; Foretz, Marc and Kiens, Bente , et al. (2023) In Obesity 31(10). p.2515-2529
Abstract

OBJECTIVE: Salt-inducible kinase 2 (SIK2) is abundantly expressed in adipocytes and downregulated in adipose tissue from individuals with obesity or insulin resistance. The main aims of this work were to investigate the involvement of SIKs in the regulation of glucose uptake in primary mature human adipocytes and to identify mechanisms underlying this regulation.

METHODS: Primary mature adipocytes were isolated from human, rat, or mouse adipose tissue and treated with pan-SIK inhibitors. Adipocytes isolated from wild type, ob/ob, and SIK2 knockout mice were also used. Glucose uptake was examined by glucose tracer assay. The insulin signaling pathway was monitored by Western blotting, co-immunoprecipitation, and total internal... (More)

OBJECTIVE: Salt-inducible kinase 2 (SIK2) is abundantly expressed in adipocytes and downregulated in adipose tissue from individuals with obesity or insulin resistance. The main aims of this work were to investigate the involvement of SIKs in the regulation of glucose uptake in primary mature human adipocytes and to identify mechanisms underlying this regulation.

METHODS: Primary mature adipocytes were isolated from human, rat, or mouse adipose tissue and treated with pan-SIK inhibitors. Adipocytes isolated from wild type, ob/ob, and SIK2 knockout mice were also used. Glucose uptake was examined by glucose tracer assay. The insulin signaling pathway was monitored by Western blotting, co-immunoprecipitation, and total internal reflection fluorescence microscopy.

RESULTS: This study demonstrates that SIK2 is downregulated in obese ob/ob mice and that SIK activity is required for intact glucose uptake in primary human and mouse adipocytes. The underlying mechanism involves direct effects on the insulin signaling pathway, likely at the level of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) generation or breakdown. Moreover, lack of SIK2 alone is sufficient to attenuate glucose uptake in mouse adipocytes.

CONCLUSIONS: SIK2 is required for insulin action in human adipocytes, and the mechanism includes direct effects on the insulin signaling pathway.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Obesity
volume
31
issue
10
pages
2515 - 2529
publisher
Nature Publishing Group
external identifiers
  • scopus:85168562004
  • pmid:37608474
ISSN
1930-739X
DOI
10.1002/oby.23858
project
Salt-inducible kinases in adipose tissue
language
English
LU publication?
yes
additional info
© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.
id
9277b393-55a0-474e-bd3d-e8fcffaeae2c
date added to LUP
2023-08-28 06:06:29
date last changed
2024-04-20 02:41:17
@article{9277b393-55a0-474e-bd3d-e8fcffaeae2c,
  abstract     = {{<p>OBJECTIVE: Salt-inducible kinase 2 (SIK2) is abundantly expressed in adipocytes and downregulated in adipose tissue from individuals with obesity or insulin resistance. The main aims of this work were to investigate the involvement of SIKs in the regulation of glucose uptake in primary mature human adipocytes and to identify mechanisms underlying this regulation.</p><p>METHODS: Primary mature adipocytes were isolated from human, rat, or mouse adipose tissue and treated with pan-SIK inhibitors. Adipocytes isolated from wild type, ob/ob, and SIK2 knockout mice were also used. Glucose uptake was examined by glucose tracer assay. The insulin signaling pathway was monitored by Western blotting, co-immunoprecipitation, and total internal reflection fluorescence microscopy.</p><p>RESULTS: This study demonstrates that SIK2 is downregulated in obese ob/ob mice and that SIK activity is required for intact glucose uptake in primary human and mouse adipocytes. The underlying mechanism involves direct effects on the insulin signaling pathway, likely at the level of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) generation or breakdown. Moreover, lack of SIK2 alone is sufficient to attenuate glucose uptake in mouse adipocytes.</p><p>CONCLUSIONS: SIK2 is required for insulin action in human adipocytes, and the mechanism includes direct effects on the insulin signaling pathway.</p>}},
  author       = {{Säll, Johanna and Lindahl, Maria and Fritzen, Andreas M and Fryklund, Claes and Kopietz, Franziska and Nyberg, Emma and Warvsten, Anna and Morén, Björn and Foretz, Marc and Kiens, Bente and Stenkula, Karin G and Göransson, Olga}},
  issn         = {{1930-739X}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{10}},
  pages        = {{2515--2529}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Obesity}},
  title        = {{Salt-inducible kinases are required for glucose uptake and insulin signaling in human adipocytes}},
  url          = {{http://dx.doi.org/10.1002/oby.23858}},
  doi          = {{10.1002/oby.23858}},
  volume       = {{31}},
  year         = {{2023}},
}