ArticleCell metabolism2012
Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity.
Article in Cell metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 212 citations in OpenAlex.
- RNA-independent cis-autoregulatory circuits within bidirectional gene pairs control metabolism.Science advances · 2026Article
- Grain proteins ameliorate glucose metabolism disorders by activating intestinal AhR and the hepatic NLK/FOXO1 pathway via gut microbiota-derived indole metabolites.Journal of advanced research · 2026Article
- Modulation of the tumor microenvironment by incretins and glucagon: Metabolic and immune mechanisms (Review).Experimental and therapeutic medicine · 2026Review
- Endocrine regulation of the hepatic fasting response: cues, cooperation and consequences.Nature reviews. Endocrinology · 2026Review
- Studies of Foxo1 over the Past 25 Years: Mechanisms of Insulin Resistance and Glucose Dysregulation.Cells · 2026Review
- CHIP mediates glucagon action on hepatic glucose production via regulating Smad3 ubiquitination.Diabetes, obesity & metabolism · 2025Article
- EHBP1 suppresses liver fibrosis in metabolic dysfunction-associated steatohepatitis.Cell metabolism · 2025Article
- Establishing the relationships between obesity and genetically predicted serum micronutrient levels: a multivariable Mendelian randomization analysis.Eating and weight disorders : EWD · 2025Article
- CAMKIIδ Reinforces Lipid Metabolism and Promotes the Development of B Cell Lymphoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A comparative genomic study across 396 liver biopsies provides deep insight into FGF21 mode of action as a therapeutic agent in metabolic dysfunction-associated steatotic liver disease.Clinical and translational medicine · 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
- Cytosolic calcium regulates hepatic mitochondrial oxidation, intrahepatic lipolysis, and gluconeogenesis via CAMKII activation.Cell metabolism · 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
- Role of CaMKII in diabetes induced vascular injury and its interaction with anti-diabetes therapy.Reviews in endocrine & metabolic disorders · 2024Review
- Integration of metabolic flux with hepatic glucagon signaling and gene expression profiles in the conscious dog.American journal of physiology. Endocrinology and metabolism · 2024Article
- Protein Kinases in Obesity, and the Kinase-Targeted Therapy.Advances in experimental medicine and biology · 2024Review
- Unveiling dynamic hepatocyte plasticity in HepaRG cells with a dual CYP reporter system.PloS one · 2024Article
- CPS1 augments hepatic glucagon response through CaMKII/FOXO1 pathway.Frontiers in pharmacology · 2024Article
- Review
80 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Hepatic glucose production (HGP) is crucial for glucose homeostasis, but the underlying mechanisms have not been fully elucidated. Here, we show that a calcium-sensing enzyme, CaMKII, is activated in a calcium- and IP3R-dependent manner by cAMP and glucagon in primary hepatocytes and by glucagon and fasting in vivo. Genetic deficiency or inhibition of CaMKII blocks nuclear translocation of FoxO1 by affecting its phosphorylation, impairs fasting- and glucagon/cAMP-induced glycogenolysis and gluconeogenesis, and lowers blood glucose levels, while constitutively active CaMKII has the opposite effects. Importantly, the suppressive effect of CaMKII deficiency on glucose metabolism is abrogated by transduction with constitutively nuclear FoxO1, indicating that the effect of CaMKII deficiency requires nuclear exclusion of FoxO1. This same pathway is also involved in excessive HGP in the setting of obesity. These results reveal a calcium-mediated signaling pathway involved in FoxO1 nuclear localization and hepatic glucose homeostasis.
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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.