ArticleCell metabolism2013
Activation of calcium/calmodulin-dependent protein kinase II in obesity mediates suppression of hepatic insulin signaling.
Article in Cell metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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Who cites it
79 citing papers in PubMed, 133 citations in OpenAlex.
- Hepatic PDIA5 improves hyperglycaemia and insulin resistance through stabilisation of ATF6.Diabetologia · 2026Article
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- The role of mitochondrial-associated endoplasmic reticulum membranes (MAMs) in diabetic microvascular complications: a review.Cell death & disease · 2025Review
- Impaired CAMK4 Activity Limits Atherosclerosis and Reprograms Myelopoiesis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- ROS-Activated TRPM2 Channel: Calcium Homeostasis in Cardiovascular/renal System and Speculation in Cardiorenal Syndrome.Cardiovascular drugs and therapy · 2025Review
- Role of LMCD1 in the Long-Term Effects of Angiotensin II in Vascular Smooth Muscle Cells.International journal of molecular sciences · 2025Article
- Ethyl acetate extract ofFrontiers in pharmacology · 2025Article
- Calcium/Calmodulin-Dependent Protein Kinase II Inhibitors Mitigate High-Fat Diet-Induced Obesity in Mice.Journal of obesity · 2025Article
- An Nrf2-NF-κB Crosstalk Controls Hepatocyte Proliferation in the Normal and Injured Liver.Cellular and molecular gastroenterology and hepatology · 2025Article
- MIST1 regulates endoplasmic reticulum stress-induced hepatic apoptosis as a candidate marker of fatty liver disease progression.Cell death & disease · 2024Article
- Identification of the Beta Subunit Fas1p of Fatty Acid Synthetase as an Interacting Partner of Yeast Calcium/Calmodulin-Dependent Protein Kinase Cmk2p Through Mass Spectrometry Analysis.Applied biochemistry and biotechnology · 2024Article
- Adiposity, immunity, and inflammation: interrelationships in health and disease: a report from 24th Annual Harvard Nutrition Obesity Symposium, June 2023.The American journal of clinical nutrition · 2024Article
- Thromboxane AAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- miRNA levels are associated with body mass index in endometrial cancer and may have implications for therapy.Cancer science · 2024Article
- Dietary Tomato Pectin Attenuates Hepatic Insulin Resistance and Inflammation in High-Fat-Diet Mice by Regulating the PI3K/AKT Pathway.Foods (Basel, Switzerland) · 2024Article
- Protein Kinases in Obesity, and the Kinase-Targeted Therapy.Advances in experimental medicine and biology · 2024Review
- A Liquid Biopsy-Based Approach to Isolate and Characterize Adipose Tissue-Derived Extracellular Vesicles from Blood.ACS nano · 2023Article
- Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
A hallmark of obesity is selective suppression of hepatic insulin signaling ("insulin resistance"), but critical gaps remain in our understanding of the molecular mechanisms. We now report a major role for hepatic CaMKII, a calcium-responsive kinase that is activated in obesity. Genetic targeting of hepatic CaMKII, its downstream mediator p38, or the p38 substrate and stabilizer MK2 enhances insulin-induced p-Akt in palmitate-treated hepatocytes and obese mouse liver, leading to metabolic improvement. The mechanism of improvement begins with induction of ATF6 and the ATF6 target p58(IPK), a chaperone that suppresses the PERK-p-eIF2α-ATF4 branch of the UPR. The result is a decrease in the ATF4 target TRB3, an inhibitor of insulin-induced p-Akt, leading to enhanced activation of Akt and its downstream metabolic mediators. These findings increase our understanding of the molecular mechanisms linking obesity to selective insulin resistance and suggest new therapeutic targets for type 2 diabetes and metabolic syndrome.
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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.