ArticleMolecular metabolism2016
Skeletal muscle salt inducible kinase 1 promotes insulin resistance in obesity.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Liposome-encapsulated AICAR hydrogel regulates macrophage metabolic reprogramming via SIK1 activation to alleviate osteoarthritis.Journal of nanobiotechnology · 2025Article
- Salt-inducible Kinase Regulation of Adipose Tissue Metabolism.Endocrinology · 2025Review
- 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
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
- Hepatic ZBTB22 promotes hyperglycemia and insulin resistance via PEPCK1-driven gluconeogenesis.EMBO reports · 2023Article
- A parathyroid hormone/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis.The Journal of clinical investigation · 2023Article
- Article
- Linking Mitochondrial Function to Insulin Resistance: Focusing on Comparing the Old and the Young.Frontiers in nutrition · 2022Article
- Pannexin 1 channels facilitate communication between T cells to restrict the severity of airway inflammation.Immunity · 2021Article
- Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption.eLife · 2021Article
- In vivo screen identifies a SIK inhibitor that induces β cell proliferation through a transient UPR.Nature metabolism · 2021Article
- Nuts and bolts of the salt-inducible kinases (SIKs).The Biochemical journal · 2021Review
- HDAC4 Knockdown Alleviates Denervation-Induced Muscle Atrophy by Inhibiting Myogenin-Dependent Atrogene Activation.Frontiers in cellular neuroscience · 2021Article
- Risperidone Mitigates Enhanced Excitatory Neuronal Function and Repetitive Behavior Caused by an ASD-Associated Mutation of SIK1.Frontiers in molecular neuroscience · 2021Article
- Article
- Activation of SIK1 by phanginin A inhibits hepatic gluconeogenesis by increasing PDE4 activity and suppressing the cAMP signaling pathway.Molecular metabolism · 2020Article
- The potent roles of salt-inducible kinases (SIKs) in metabolic homeostasis and tumorigenesis.Signal transduction and targeted therapy · 2020Review
- Lack of skeletal muscle liver kinase B1 alters gene expression, mitochondrial content, inflammation and oxidative stress without affecting high-fat diet-induced obesity or insulin resistance.Biochimica et biophysica acta. Molecular basis of disease · 2020Article
- Loss of the conserved PKA sites of SIK1 and SIK2 increases sleep need.Scientific reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveInsulin resistance causes type 2 diabetes mellitus and hyperglycemia due to excessive hepatic glucose production and inadequate peripheral glucose uptake. Our objectives were to test the hypothesis that the proposed CREB/CRTC2 inhibitor salt inducible kinase 1 (SIK1) contributes to whole body glucose homeostasis in vivo by regulating hepatic transcription of gluconeogenic genes and also to identify novel SIK1 actions on glucose metabolism.
methodsWe created conditional (floxed) SIK1-knockout mice and studied glucose metabolism in animals with global, liver, adipose or skeletal muscle Sik1 deletion. We examined cAMP-dependent regulation of SIK1 and the consequences of SIK1 depletion on primary mouse hepatocytes. We probed metabolic phenotypes in tissue-specific SIK1 knockout mice fed high fat diet through hyperinsulinemic-euglycemic clamps and biochemical analysis of insulin signaling.
resultsSIK1 knockout mice are viable and largely normoglycemic on chow diet. On high fat diet, global SIK1 knockout animals are strikingly protected from glucose intolerance, with both increased plasma insulin and enhanced peripheral insulin sensitivity. Surprisingly, liver SIK1 is not required for regulation of CRTC2 and gluconeogenesis, despite contributions of SIK1 to hepatocyte CRTC2 and gluconeogenesis regulation ex vivo. Sik1 mRNA accumulates in skeletal muscle of obese high fat diet-fed mice, and knockout of SIK1 in skeletal muscle, but not liver or adipose tissue, improves insulin sensitivity and muscle glucose uptake on high fat diet.
conclusionsSIK1 is dispensable for glycemic control on chow diet. SIK1 promotes insulin resistance on high fat diet by a cell-autonomous mechanism in skeletal muscle. Our study establishes SIK1 as a promising therapeutic target to improve skeletal muscle insulin sensitivity in obese individuals without deleterious effects on hepatic glucose production.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.