ArticleThe Journal of clinical endocrinology and metabolism2020
Kinome Profiling Reveals Abnormal Activity of Kinases in Skeletal Muscle From Adults With Obesity and Insulin Resistance.
Article in The Journal of clinical endocrinology and metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Article
- Mechanomedicine for Addressing Skeletal Muscle Insulin Resistance.Endocrine reviews · 2025Review
- Metformin inhibits the proliferation of hepatocellular carcinoma cells through inducing ferroptosis analyzed by phosphoproteomics.Frontiers in oncology · 2025Article
- Roles of naïve CD4Journal of translational medicine · 2024Article
- Glucose restriction enhances oxidative fiber formation: A multi-omic signal network involving AMPK and CaMK2.iScience · 2024Article
- Integrated proteome and phosphoproteome analysis of gastric adenocarcinoma reveals molecular signatures capable of stratifying patient outcome.Molecular oncology · 2023Article
- Reduced Tyrosine and Serine-632 Phosphorylation of Insulin Receptor Substrate-1 in the Gastrocnemius Muscle of Obese Zucker Rat.Current issues in molecular biology · 2022Article
- Article
- Profiling the Skeletal Muscle Proteome in Patients on Atypical Antipsychotics and Mood Stabilizers.Brain sciences · 2022Article
- Metformin Increases Protein Phosphatase 2A Activity in Primary Human Skeletal Muscle Cells Derived from Lean Healthy Participants.Journal of diabetes research · 2021Article
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Authors and funding
17 authors at 2 institutions in 3 countries.
Funding
Abstract
contextObesity-related insulin resistance (OIR) is one of the main contributors to type 2 diabetes and other metabolic diseases. Protein kinases are implicated in insulin signaling and glucose metabolism. Molecular mechanisms underlying OIR involving global kinase activities remain incompletely understood.
objectiveTo investigate abnormal kinase activity associated with OIR in human skeletal muscle.
designUtilization of stable isotopic labeling-based quantitative proteomics combined with affinity-based active enzyme probes to profile in vivo kinase activity in skeletal muscle from lean control (Lean) and OIR participants.
participantsA total of 16 nondiabetic adults, 8 Lean and 8 with OIR, underwent hyperinsulinemic-euglycemic clamp with muscle biopsy.
resultsWe identified the first active kinome, comprising 54 active protein kinases, in human skeletal muscle. The activities of 23 kinases were different in OIR muscle compared with Lean muscle (11 hyper- and 12 hypo-active), while their protein abundance was the same between the 2 groups. The activities of multiple kinases involved in adenosine monophosphate-activated protein kinase (AMPK) and p38 signaling were lower in OIR compared with Lean. On the contrary, multiple kinases in the c-Jun N-terminal kinase (JNK) signaling pathway exhibited higher activity in OIR vs Lean. The kinase-substrate-prediction based on experimental data further confirmed a potential downregulation of insulin signaling (eg, inhibited phosphorylation of insulin receptor substrate-1 and AKT1/2).
conclusionsThese findings provide a global view of the kinome activity in OIR and Lean muscle, pinpoint novel specific impairment in kinase activities in signaling pathways important for skeletal muscle insulin resistance, and may provide potential drug targets (ie, abnormal kinase activities) to prevent and/or reverse skeletal muscle insulin resistance in humans.
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