ArticleCell death & disease2016
SP6616 as a new Kv2.1 channel inhibitor efficiently promotes β-cell survival involving both PKC/Erk1/2 and CaM/PI3K/Akt signaling pathways.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
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- Identification and mechanistic insights of ubiquitin-proteasome system and pyroptosis-related biomarkers in type 2 diabetes mellitus.World journal of diabetes · 2025Article
- Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment.International journal of molecular medicine · 2025Article
- Drofenine as a Kv2.1 inhibitor alleviated AD-like pathology in mice through AActa pharmaceutica Sinica. B · 2025Article
- Molecular mechanism responsible for sex differences in electrical activity of mouse pancreatic β cells.JCI insight · 2024Article
- Downregulation of the silent potassium channel Kv8.1 increases motor neuron vulnerability in amyotrophic lateral sclerosis.Brain communications · 2024Article
- Molecular study of the proliferation process of beta cells derived from pluripotent stem cells.Molecular biology reports · 2022Review
- Voltage-gated potassium channels are involved in oxymatrine-regulated islet function in rat islet β cells and INS-1 cells.Iranian journal of basic medical sciences · 2021Article
- Telmisartan Potentiates Insulin Secretion via Ion Channels, Independent of the AT1 Receptor and PPARγ.Frontiers in pharmacology · 2021Article
- Sphingosine 1-phosphate Stimulates Insulin Secretion and Improves Cell Survival by Blocking Voltage-dependent KFrontiers in pharmacology · 2021Article
- Therapeutic Potential of Peptides Derived from Animal Venoms: Current Views and Emerging Drugs for Diabetes.Clinical medicine insights. Endocrinology and diabetes · 2021Review
- SP6616 as a Kv2.1 inhibitor efficiently ameliorates peripheral neuropathy in diabetic mice.EBioMedicine · 2020Article
- Antispasmodic Drug Drofenine as an Inhibitor of Kv2.1 Channel Ameliorates Peripheral Neuropathy in Diabetic Mice.iScience · 2020Article
- Voltage-Gated Potassium Channels as Regulators of Cell Death.Frontiers in cell and developmental biology · 2020Review
- Small molecule IVQ, as a prodrug of gluconeogenesis inhibitor QVO, efficiently ameliorates glucose homeostasis in type 2 diabetic mice.Acta pharmacologica Sinica · 2019Article
- Potential independent action of sigma receptor ligands through inhibition of the Kv2.1 channel.Oncotarget · 2017Article
- Calmodulin and PI3K Signaling inTrends in cancer · 2017Review
- Osthole Protects Bone Marrow-Derived Neural Stem Cells from Oxidative Damage through PI3K/Akt-1 Pathway.Neurochemical research · 2017Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kv2.1 as a voltage-gated potassium (Kv) channel subunit has a pivotal role in the regulation of glucose-stimulated insulin secretion (GSIS) and pancreatic β-cell apoptosis, and is believed to be a promising target for anti-diabetic drug discovery, although the mechanism underlying the Kv2.1-mediated β-cell apoptosis is obscure. Here, the small molecular compound, ethyl 5-(3-ethoxy-4-methoxyphenyl)-2-(4-hydroxy-3-methoxybenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate (SP6616) was discovered to be a new Kv2.1 inhibitor. It was effective in both promoting GSIS and protecting β cells from apoptosis. Evaluation of SP6616 on either high-fat diet combined with streptozocin-induced type 2 diabetic mice or db/db mice further verified its efficacy in the amelioration of β-cell dysfunction and glucose homeostasis. SP6616 treatment efficiently increased serum insulin level, restored β-cell mass, decreased fasting blood glucose and glycated hemoglobin levels, and improved oral glucose tolerance. Mechanism study indicated that the promotion of SP6616 on β-cell survival was tightly linked to its regulation against both protein kinases C (PKC)/extracellular-regulated protein kinases 1/2 (Erk1/2) and calmodulin(CaM)/phosphatidylinositol 3-kinase(PI3K)/serine/threonine-specific protein kinase (Akt) signaling pathways. To our knowledge, this may be the first report on the underlying pathway responsible for the Kv2.1-mediated β-cell protection. In addition, our study has also highlighted the potential of SP6616 in the treatment of type 2 diabetes.
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