Salt-inducible kinases in adipose tissue
Signalvägar i fettceller av betydelse för uppkomsten av fetma och typ 2 diabetes
Author
Summary, in English
We demonstrate that the transcriptional regulators CRTC2, CRTC3 and HDAC4 are direct downstream substrates of SIK2 in adipocytes. Moreover, we demonstrate that the expression of SIK2 and SIK3 is markedly downregulated in adipose tissue from obese or insulin-resistant individuals. Furthermore, the expression of SIK2 and SIK3 in adipose tissue is regulated in response to weight change and inflammation (TNF-α). SIKs are involved in promoting glucose uptake in adipocytes and the underlying mechanism(s) involves direct, and positive, effects on the insulin signalling pathway. We also identify a novel regulatory pathway of SIK2 in adipocytes through insulin-induced phosphorylation at Thr484. From a functional aspect, insulin stimulation appears to be important to increase SIK2 protein stability. Taken together, our data suggest that insulin resistance might be a causal factor underlying the downregulation of SIK2 in human adipose tissue. Given these findings, SIK2 might provide an attractive therapeutic target for the treatment of metabolic diseases in the future. Importantly, our findings on SIK2 expression in human obesity and insulin resistance are in contrast to what was previously identified in mice, and demonstrates that interspecies differences exist with regard to the regulation of SIK2 in metabolic disease. Furthermore, this emphasise the importance to study SIKs in human adipocytes.
Publishing year
2017
Language
English
Full text
Document type
Dissertation
Publisher
Lund University: Faculty of Medicine
Topic
- Basic Medicine
Keywords
- salt-inducible kinase
- SIK
- SIK2
- fettväv
- fettceller
- insulinsignalering
- glukosupptag
- fetma
- insulinresistens
- salt-inducible kinase
- SIK
- SIK2
- adipose tissue
- adipocytes
- insulin signalling
- glucose uptake
- obesity
- insulin resistance
Status
Published
Research group
- Protein Phosphorylation
Supervisor
ISBN/ISSN/Other
- ISBN: 978-91-7619-513-0
Defence date
5 September 2017
Defence time
09:00
Defence place
Segerfalksalen, BMC A10, Sölvegatan 17, Lund
Opponent
- Margit Mahlapuu (docent)