ArticleMolecular metabolism2015
Decreased expression of hepatic glucokinase in type 2 diabetes.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Balancing efficacy and safety: glucokinase activators in glycemic and metabolic management of type 2 diabetes mellitus-a meta-analysis.Endocrine journal · 2025Pooled it
- Effects of Dorzagliatin, a Glucokinase Activator, on α- and β-Cell Function in Individuals With Impaired and Normal Glucose Tolerance.Diabetes · 2025Trial
- Trial
- Dorzagliatin in drug-naïve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.Nature medicine · 2022Trial
- Acute AKT signaling increases glucose phosphorylation and contribution to glycogen in hepatocytes.iScience · 2026Article
- Gut dysbiosis induced by sunflower oil-based sucrose-free high-fat diet leads to steatohepatitis.Frontiers in nutrition · 2026Article
- Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways.Clinical science (London, England : 1979) · 2025Review
- Factors influencing the initial glycemic efficacy of dorzagliatin, a novel glucokinase activator, in type 2 diabetes.Endocrine · 2025Article
- The neglected PCK1/glucagon (inter)action in nutrient homeostasis beyond gluconeogenesis: Disease pathogenesis and treatment.Molecular metabolism · 2025Review
- Article
- Modern Challenges in Type 2 Diabetes: Balancing New Medications with Multifactorial Care.Biomedicines · 2024Review
- The role of adipose tissue dysfunction in hepatic insulin resistance and T2D.The Journal of endocrinology · 2024Review
- Novel Therapeutics for Type 2 Diabetes Mellitus-A Look at the Past Decade and a Glimpse into the Future.Biomedicines · 2024Review
- Clinical investigation of glucokinase activators for the restoration of glucose homeostasis in diabetes.Journal of diabetes · 2024Review
- Should Glucokinase be Given a Chance in Diabetes Therapeutics? A Clinical-Pharmacological Review of Dorzagliatin and Lessons Learned So Far.Clinical drug investigation · 2024Review
- Nano-Stevia reduces the liver injury caused by streptozotocin (STZ)-induced diabetes in rats by targeting PEPCK/GCK genes, INSR pathway and apoptosis.Journal of diabetes and metabolic disorders · 2023Article
- Glucokinase and glucokinase activator.Life metabolism · 2023Review
- β-Cell glucokinase expression was increased in type 2 diabetes subjects with better glycemic control.Journal of diabetes · 2023Article
- Article
- A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity.Nature communications · 2023Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
objectivesIncreased endogenous glucose production is a hallmark of type 2 diabetes. Evidence from animal models has suggested that a likely cause of this is increased mRNA expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase (encoded by G6PC, PCK1 and PCK2). But another contributing factor may be decreased liver glucokinase (encoded by GCK).
methodsWe examined expression of these enzymes in liver biopsies from 12 nondiabetic and 28 diabetic individuals. Diabetic patients were further separated into those with HbA1c lower or higher than 7.0.
resultsIn diabetic subjects with HbA1c > 7.0, we found that gluconeogenic enzymes were expressed normally, but GCK was suppressed more than 60%. Moreover, HbA1c and fasting glucose were negatively correlated with GCK, but showed no correlation with G6PC, PCK1, or PCK2.
conclusionThese findings suggest an underlying dysregulation of hepatic GCK expression during frank diabetes, which has implications for the therapeutic use of glucokinase activators in this population.
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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.