ArticleDiabetologia2003
Long-term overexpression of glucokinase in the liver of transgenic mice leads to insulin resistance.
Article in Diabetologia, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 111 citations in OpenAlex.
- Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients with type 2 diabetes.Diabetes care · 2011 · on this mapTrial
- Liver-specific actions of GH and IGF1 that protect against MASLD.Nature reviews. Endocrinology · 2025 · on this mapReview
- Glucokinase (GCK) in diabetes: from molecular mechanisms to disease pathogenesis.Cellular & molecular biology letters · 2024Review
- Intermittent fasting protects β-cell identity and function in a type-2 diabetes model.Metabolism: clinical and experimental · 2024Article
- Should Glucokinase be Given a Chance in Diabetes Therapeutics? A Clinical-Pharmacological Review of Dorzagliatin and Lessons Learned So Far.Clinical drug investigation · 2024Review
- Inter-Organ Communication Involved in Brown Adipose Tissue Thermogenesis.Advances in experimental medicine and biology · 2024Review
- Obesity-associated microglial inflammatory activation paradoxically improves glucose tolerance.Cell metabolism · 2023Article
- Direct and systemic actions of growth hormone receptor (GHR)-signaling on hepatic glycolysis, de novo lipogenesis and insulin sensitivity, associated with steatosis.Metabolism: clinical and experimental · 2023Article
- A Keystone Gut BacteriumFoods (Basel, Switzerland) · 2023Review
- 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
- Glucokinase regulatory protein: a balancing act between glucose and lipid metabolism in NAFLD.Frontiers in endocrinology · 2023Review
- Novel Plant Extract Ameliorates Metabolic Disorder through Activation of Brown Adipose Tissue in High-Fat Diet-Induced Obese Mice.International journal of molecular sciences · 2022Article
- Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats.Frontiers in nutrition · 2022Article
- Targeting hepatocyte carbohydrate transport to mimic fasting and calorie restriction.The FEBS journal · 2021Review
- A New Strain ofCells · 2021Article
- A new clinical screening strategy and prevalence estimation for glucokinase variant-induced diabetes in an adult Chinese population.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Hepatic HKDC1 Expression Contributes to Liver Metabolism.Endocrinology · 2019Article
- Bivariate Genome-Wide Association Scan Identifies 6 Novel Loci Associated With Lipid Levels and Coronary Artery Disease.Circulation. Genomic and precision medicine · 2018Article
- Krüppel-like factors: Crippling and un-crippling metabolic pathways.JACC. Basic to translational science · 2018Article
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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
aims/hypothesisGlucokinase overexpression in the liver increases glucose uptake and utilization, and improves glucose tolerance in young transgenic mice. Here, we examined the long-term effects of hepatic overexpression of glucokinase on glucose homeostasis. Moreover, we determined whether glucokinase overexpression counteracted high-fat diet-induced insulin resistance.
methodsTransgenic mice overexpressing glucokinase in liver under the control of the phosphoenolpyruvate carboxykinase promoter, fed either a standard diet or a high-fat diet, were studied. We used non-transgenic littermates as controls.
resultsTransgenic mice over 6 months old developed impaired glucose tolerance. In addition, at 12 months of age, transgenic mice showed mild hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia. In spite of increased glucokinase activity, the liver of these mice accumulated less glycogen and increased triglyceride deposition. When 2-month-old glucose-tolerant mice were fed a high-fat diet, transgenic mice gained more body weight and became hyperglycaemic and hyperinsulinaemic. This was concomitant to glucose intolerance, liver steatosis and whole-body insulin resistance. CONCLUSION/
interpretationLong-term overexpression of glucokinase increases hepatic lipogenesis and circulating lipids, which lead to insulin resistance. Our results also suggest that the liver plays a key role in the onset of diabetes.
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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.