ArticleScientific reports2015
Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- GCKR Polymorphisms Increase the Risks of Low Bone Mineral Density in Young and Non-Obese Patients With MASLD and Hyperuricemia.The Kaohsiung journal of medical sciences · 2025Article
- Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC.Frontiers in pharmacology · 2025Review
- Glucokinase (GCK) in diabetes: from molecular mechanisms to disease pathogenesis.Cellular & molecular biology letters · 2024Review
- Interplay of Mediterranean-diet adherence, genetic factors, and metabolic dysfunction-associated steatotic liver disease risk in Korea.Journal of translational medicine · 2024Article
- Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.Clinical epigenetics · 2024Review
- Current Insight on the Role of Glucokinase and Glucokinase Regulatory Protein in Diabetes.Mini reviews in medicinal chemistry · 2024Review
- The GCKR-P446L gene variant predisposes to raised blood cholesterol and lower blood glucose in the P446L mouse-a model for GCKR rs1260326.Molecular metabolism · 2023Article
- Roles of KLF4 and AMPK in the inhibition of glycolysis by pulsatile shear stress in endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- SIRT2 ablation inhibits glucose-stimulated insulin secretion through decreasing glycolytic flux.Theranostics · 2021Article
- Functional Characterization of a Novel Heterozygous Mutation in the Glucokinase Gene That Causes MODY2 in Chinese Pedigrees.Frontiers in endocrinology · 2021Article
- ROS-Induced SIRT2 Upregulation Contributes to Cisplatin Sensitivity in Ovarian Cancer.Antioxidants (Basel, Switzerland) · 2020Article
- L-Arginine prevents cereblon-mediated ubiquitination of glucokinase and stimulates glucose-6-phosphate production in pancreatic β-cells.Communications biology · 2020Article
- Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats.Frontiers in endocrinology · 2020Article
- Enzymatic and nonenzymatic protein acetylations control glycolysis process in liver diseases.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Review
- Exogenous HAmerican journal of physiology. Endocrinology and metabolism · 2019Article
- Molecular and cellular regulation of human glucokinase.Archives of biochemistry and biophysics · 2019Review
- A Journey to Understand Glucose Homeostasis: Starting from Rat Glucose Transporter Type 2 Promoter Cloning to Hyperglycemia.Diabetes & metabolism journal · 2018Review
- Metabolites as regulators of insulin sensitivity and metabolism.Nature reviews. Molecular cell biology · 2018Review
- The Flavonoid Kaempferol Ameliorates Streptozotocin-Induced Diabetes by Suppressing Hepatic Glucose Production.Molecules (Basel, Switzerland) · 2018Article
- Sirt2 facilitates hepatic glucose uptake by deacetylating glucokinase regulatory protein.Nature communications · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucokinase (GK), mainly expressed in the liver and pancreatic β-cells, is critical for maintaining glucose homeostasis. GK expression and kinase activity, respectively, are both modulated at the transcriptional and post-translational levels. Post-translationally, GK is regulated by binding the glucokinase regulatory protein (GKRP), resulting in GK retention in the nucleus and its inability to participate in cytosolic glycolysis. Although hepatic GKRP is known to be regulated by allosteric mechanisms, the precise details of modulation of GKRP activity, by post-translational modification, are not well known. Here, we demonstrate that GKRP is acetylated at Lys5 by the acetyltransferase p300. Acetylated GKRP is resistant to degradation by the ubiquitin-dependent proteasome pathway, suggesting that acetylation increases GKRP stability and binding to GK, further inhibiting GK nuclear export. Deacetylation of GKRP is effected by the NAD(+)-dependent, class III histone deacetylase SIRT2, which is inhibited by nicotinamide. Moreover, the livers of db/db obese, diabetic mice also show elevated GKRP acetylation, suggesting a broader, critical role in regulating blood glucose. Given that acetylated GKRP may affiliate with type-2 diabetes mellitus (T2DM), understanding the mechanism of GKRP acetylation in the liver could reveal novel targets within the GK-GKRP pathway, for treating T2DM and other metabolic pathologies.
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