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In silico design of dehydrophenylalanine containing peptide activators of glucokinase using pharmacophore modelling, molecular dynamics and machine learning: implications in type 2 diabetes.
J Comput Aided Mol Des
December 2024
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Sector-125, Noida, UP, 201313, India.
Article Synopsis
- Diabetes is a significant global health issue that involves high healthcare costs and complex treatments, leading to the search for new medication options due to the side effects of current therapies.
- Glucokinase (GK) plays a crucial role in regulating blood sugar levels and has unique properties that make it a good target for type-2 diabetes treatment; glucokinase activators (GKAs) can enhance GK activity, but safety concerns persist with existing options.
- A study developed a new type of GKA using peptide-based compounds with unique amino acids, discovering three promising peptides that increase GK activity significantly; machine learning techniques were also employed to predict their effectiveness.
Genetic Variants in Severe Hypertriglyceridemia Among Taiwanese Participants - Insights From Genome-Wide Association and Whole-Exome Sequencing Analyses.
Circ J
December 2024
Institute of Epidemiology and Preventive Medicine, National Taiwan University.
Article Synopsis
- A study explored whole-exome sequencing (WES) to better understand severe hypertriglyceridemia by identifying genes linked to high triglyceride levels through a genome-wide association study (GWAS).
- The GWAS involved over 120,000 participants and found that the APOA5 locus on chromosome 11 has the strongest association with triglyceride levels, alongside other significant genes like BUD13, GCKR, and LPL.
- WES conducted on 29 patients with extreme hypertriglyceridemia identified additional genes such as ALDH1A2 and APOC1, highlighting both known and novel genetic factors that may influence lipid metabolism and open up possibilities for new treatments.
Glucokinase activators and imeglimin: new weaponry in the armamentarium against type 2 diabetes.
BMJ Open Diabetes Res Care
August 2024
University of Gävle, Gavle, Sweden
The prevalence of type 2 diabetes (T2D) is increasing relentlessly all over the world, in parallel with a similar increase in obesity, and is striking ever younger patients. Only a minority of patients with T2D attain glycemic targets, indicating a clear need for novel antidiabetic drugs that not only control glycemia but also halt or slow the progressive loss of β-cells. Two entirely novel classes of antidiabetic agents-glucokinase activators and imeglimin-have recently been approved and will be the subject of this review.
View Article and Find Full Text PDFIdentification of small molecule glucokinase activators for the treatment of diabetes based on plants from the traditional Chinese medicine: In silico analysis.
Microb Pathog
October 2024
Laboratory Biochemistry Environment and Agri-food, Department of Biology, Faculty of Science and Technics Mohammedia, Hassan II University Casablanca, Morocco. Electronic address:
Mutations in glucokinase (GCK) can either enhance or inhibit insulin secretion, leading to different forms of diabetes, including gestational diabetes. While many glucokinase activators (GKAs) have been explored as treatments, their long-term effectiveness has often been unsatisfactory. However, recent interest has surged with the introduction of dorzagliatin and TTP399.
View Article and Find Full Text PDFPrediction of Protein-Drug Interactions, Pharmacophore Modeling, and Toxicokinetics of Novel Leads for Type 2 Diabetes Treatment.
Curr Drug Metab
November 2024
Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road (NH-1), Phagwara (Punjab), 144411, India.
Background: Small heterocyclic compounds have been crucial in pioneering advances in type 2 diabetes treatment. There has been a dramatic increase in the pharmacological development of novel heterocyclic derivatives aimed at stimulating the activation of Glucokinase (GK). A pharmaceutical intervention for diabetes is increasingly targeting GK as a legitimate target.
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