ArticleScientific reports2017
The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 33 citations in OpenAlex.
- Galectin-3 impairs calcium transients and β-cell function.Nature communications · 2024Article
- Design of a multi-target focused library for antidiabetic targets using a comprehensive set of chemical transformation rules.Frontiers in pharmacology · 2023Article
- Revisiting the concept of incretin and enteroendocrine L-cells as type 2 diabetes mellitus treatment.Pharmacological research · 2022Review
- Targeting the GPR119/incretin axis: a promising new therapy for metabolic-associated fatty liver disease.Cellular & molecular biology letters · 2021Review
- Targeting lipid GPCRs to treat type 2 diabetes mellitus - progress and challenges.Nature reviews. Endocrinology · 2021Review
- A Guide to Targeting the Endocannabinoid System in Drug Design.International journal of molecular sciences · 2020Review
- Multi-Target Approaches in Metabolic Syndrome.Frontiers in pharmacology · 2020Review
- DPP-4 inhibitors promote proliferation and migration of rat brain microvascular endothelial cells under hypoxic/high-glucose conditions, potentially through the SIRT1/HIF-1/VEGF pathway.CNS neuroscience & therapeutics · 2019Article
- Bidirectional GPR119 Agonism Requires Peptide YY and Glucose for Activity in Mouse and Human Colon Mucosa.Endocrinology · 2018Article
- Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1.Frontiers in endocrinology · 2018Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucagon like peptide-1 (GLP-1) plays a vital role in glucose homeostasis and sustaining β-cell function. Currently there are two major methods to enhance endogenous GLP-1 activity; inhibiting dipeptidyl peptidase-4 (DPP4) or activating G protein-coupled receptor 119 (GPR119). Here we describe and validate a novel dual-target compound, HBK001, which can both inhibit DPP4 and activate GPR119 ex and in vivo. We show that HBK001 can promote glucose-stimulated insulin secretion in mouse and human primary islets. A single administration of HBK001 in ICR mice can increase plasma incretins levels much more efficiently than linagliptin, a classic DPP4 inhibitor. Long-term treatment of HBK001 in KKAy mice can ameliorate hyperglycemia as well as improve glucose tolerance, while linagliptin fails to achieve such glucose-lowing effects despite inhibiting 95% of serum DPP4 activity. Moreover, HBK001 can increase first-phase insulin secretion in KKAy mice, suggesting a direct effect on islet β-cells via GPR119 activation. Furthermore, HBK001 can improve islet morphology, increase β-cell proliferation and up-regulate genes involved in improved β-cell function. Thus, we have identified, designed and synthesized a novel dual-target compound, HBK001, which represents a promising therapeutic candidate for type 2 diabetes, especially for patients who are insensitive to current DPP4 inhibitors.
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