ArticleDiabetologia2017
Salt-inducible kinase 2 and -3 are downregulated in adipose tissue from obese or insulin-resistant individuals: implications for insulin signalling and glucose uptake in human adipocytes.
Article in Diabetologia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- A Genome-Wide Association Study of Prediabetes Status Change.Frontiers in endocrinology · 2022Pooled it
- HDAC4: an emerging target in diabetes mellitus and diabetic complications.European journal of medical research · 2025Review
- Salt-inducible Kinase Regulation of Adipose Tissue Metabolism.Endocrinology · 2025Review
- Review
- Mapping novel QTL and fine mapping of previously identified QTL associated with glucose tolerance using the collaborative cross mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- AMPK and Beyond: The Signaling Network Controlling RabGAPs and Contraction-Mediated Glucose Uptake in Skeletal Muscle.International journal of molecular sciences · 2024Review
- Understanding the roles of salt-inducible kinases in cardiometabolic disease.Frontiers in physiology · 2024Review
- Roles of salt‑inducible kinases in cancer (Review).International journal of oncology · 2023Review
- Deficiency of salt-inducible kinase 2 (SIK2) promotes immune injury by inhibiting the maturation of lymphocytes.MedComm · 2023Article
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- Mechanism of TNFα-induced downregulation of salt-inducible kinase 2 in adipocytes.Scientific reports · 2023Article
- Designing of potent anti-diabetic molecules by targeting SIK2 using computational approaches.Molecular diversity · 2023Article
- Transcriptomic Profiling of Subcutaneous Adipose Tissue in Relation to Bariatric Surgery: A Retrospective, Pooled Re-analysis.Journal of obesity & metabolic syndrome · 2023Article
- Metabolic risk factors of ovarian cancer: a review.JBRA assisted reproduction · 2022Review
- A whole-exome case-control association study to characterize the contribution of rare coding variation to pancreatic cancer risk.HGG advances · 2022Article
- Activation of the adipocyte CREB/CRTC pathway in obesity.Communications biology · 2021Article
- Nuts and bolts of the salt-inducible kinases (SIKs).The Biochemical journal · 2021Review
- Identification of pleiotropic genes between risk factors of stroke by multivariate metaCCA analysis.Molecular genetics and genomics : MGG · 2020Article
- The potent roles of salt-inducible kinases (SIKs) in metabolic homeostasis and tumorigenesis.Signal transduction and targeted therapy · 2020Review
- Salt inducible kinases as novel Notch interactors in the developing Drosophila retina.PloS one · 2020Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisSalt-inducible kinases (SIKs) are related to the metabolic regulator AMP-activated protein kinase (AMPK). SIK2 is abundant in adipose tissue. The aims of this study were to investigate the expression of SIKs in relation to human obesity and insulin resistance, and to evaluate whether changes in the expression of SIKs might play a causal role in the development of disturbed glucose uptake in human adipocytes.
methodsSIK mRNA and protein was determined in human adipose tissue or adipocytes, and correlated to clinical variables. SIK2 and SIK3 expression and phosphorylation were analysed in adipocytes treated with TNF-α. Glucose uptake, GLUT protein levels and localisation, phosphorylation of protein kinase B (PKB/Akt) and the SIK substrate histone deacetylase 4 (HDAC4) were analysed after the SIKs had been silenced using small interfering RNA (siRNA) or inhibited using a pan-SIK-inhibitor (HG-9-91-01).
resultsWe demonstrate that SIK2 and SIK3 mRNA are downregulated in adipose tissue from obese individuals and that the expression is regulated by weight change. SIK2 is also negatively associated with in vivo insulin resistance (HOMA-IR), independently of BMI and age. Moreover, SIK2 protein levels and specific kinase activity display a negative correlation to BMI in human adipocytes. Furthermore, SIK2 and SIK3 are downregulated by TNF-α in adipocytes. Silencing or inhibiting SIK1-3 in adipocytes results in reduced phosphorylation of HDAC4 and PKB/Akt, less GLUT4 at the plasma membrane, and lower basal and insulin-stimulated glucose uptake in adipocytes. CONCLUSION/
interpretationThis is the first study to describe the expression and function of SIKs in human adipocytes. Our data suggest that SIKs might be protective in the development of obesity-induced insulin resistance, with implications for future treatment strategies.
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