ReviewDiabetes, obesity & metabolism2012
Repair of diverse diabetic defects of β-cells in man and mouse by pharmacological glucokinase activation.
Review in Diabetes, obesity & metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Efficacy and safety of dorzagliatin for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Regulation of glucagon secretion in normal and diabetic human islets by γ-hydroxybutyrate and glycine.The Journal of biological chemistry · 2013Trial
- Insights to the emerging potential of glucokinase activators as antidiabetic agent.Pharmaceutical patent analyst · 2024Review
- Lipotoxicity in a Vicious Cycle of Pancreatic Beta Cell Exhaustion.Biomedicines · 2022Article
- What Is the Metabolic Amplification of Insulin Secretion and Is It (Still) Relevant?Metabolites · 2021Review
- Review
- Nutrient sensing in pancreatic islets: lessons from congenital hyperinsulinism and monogenic diabetes.Annals of the New York Academy of Sciences · 2018Review
- Quercetin potentiates transdifferentiation of bone marrow mesenchymal stem cells into the beta cells in vitro.Journal of endocrinological investigation · 2017Article
- Safety, tolerability, pharmacokinetics, and pharmacodynamics of novel glucokinase activator HMS5552: results from a first-in-human single ascending dose study.Drug design, development and therapy · 2016Article
- Present status of clinical deployment of glucokinase activators.Journal of diabetes investigation · 2015Review
- A new compound heterozygosis for inactivating mutations in the glucokinase gene as cause of permanent neonatal diabetes mellitus (PNDM) in double-first cousins.Diabetology & metabolic syndrome · 2015Article
- Control of insulin secretion by cytochrome C and calcium signaling in islets with impaired metabolism.The Journal of biological chemistry · 2014Article
- Many faces of monogenic diabetes.Journal of diabetes investigation · 2014Review
- Normal glucose metabolism in carnivores overlaps with diabetes pathology in non-carnivores.Frontiers in endocrinology · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Glucokinase activators (GKAs) are being developed and clinically tested for potential antidiabetic therapy. The potential benefits and limitations of this approach continue to be intensively debated. To contribute to the understanding of experimental pharmacology and therapeutics of GKAs, we have tested the efficacy of one of these agents (Piragliatin) in isolated islets from humans with type 2 diabetes mellitus (T2DM), from mice with glucokinase (GK) mutations induced by ethyl-nitroso-urea (ENU) as models of Maturity Onset Diabetes of the Young linked to GK and Permanent Neonatal Diabetes Mellitus linked to GK (PNDM-GK) and finally of islets rendered glucose insensitive by treatment with the sulphonyl urea compound glyburide in organ culture. We found that the GKA repaired the defect in all three instances as manifest in increased glucose-induced insulin release and elevated intracellular calcium responses. The results show the remarkable fact that acute pharmacological activation of GK reverses secretion defects of β-cells caused by molecular mechanism that differ vastly in nature, including the little understood multifactorial lesion of β-cells in T2DM of man, the complex GK mutations in mice resembling GK disease and acute sulphonylurea failure of mouse β-cells in tissue culture. The implications of these results are to be discussed on the theoretical basis underpinning the strategy of developing these drugs and in light of recent results of clinical trials with GKAs that failed for little understood reasons.
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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.