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Chromanol 293B, an inhibitor of KCNQ1 channels, enhances glucose-stimulated insulin secretion and increases glucagon-like peptide-1 level in mice

Liu, Lijie ; Wang, Fanfan ; Lu, Haiying ; Ren, Xiaomei ; Zou, Jihong

Islets, 04 July 2014, Vol.6(4) [Peer Reviewed Journal]

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  • Title:
    Chromanol 293B, an inhibitor of KCNQ1 channels, enhances glucose-stimulated insulin secretion and increases glucagon-like peptide-1 level in mice
  • Author: Liu, Lijie ; Wang, Fanfan ; Lu, Haiying ; Ren, Xiaomei ; Zou, Jihong
  • Description: Glucose-stimulated insulin secretion (GSIS) is a highly regulated process involving complex interaction of multiple factors. Potassium voltage-gated channel subfamily KQT member 1 (KCNQ1) is a susceptibility gene for type 2 diabetes (T2D) and the risk alleles of the KCNQ1 gene appear to be associated with impaired insulin secretion. The role of KCNQ1 channel in insulin secretion has been explored by previous work in clonal pancreatic β-cells but has yet to be investigated in the context of primary islets as well as intact animals. Genetic studies suggest that altered incretin glucagon-like peptide-1 (GLP-1) secretion might be a potential link between KCNQ1 variants and impaired insulin secretion, but this hypothesis has not been verified so far. In the current study, we examined KCNQ1 expression in pancreas and intestine from normal mice and then investigated the effects of chromanol 293B, a KCNQ1 channel inhibitor, on insulin secretion in vitro and in vivo. By double-immunofluorescence staining, KCNQ1 was detected in insulin-positive β-cells and GLP-1-positive L-cells. Administration of chromanol 293B enhanced GSIS in cultured islets and intact animals. Along with the potentiated insulin secretion during oral glucose tolerance tests (OGTT), plasma GLP-1 level after gastric glucose load was increased in 293B treated mice. These data not only provided new evidence for the participation of KCNQ1 in GSIS at the level of pancreatic islet and intact animal but also indicated the potential linking role of GLP-1 between KCNQ1 and insulin secretion.
  • Is Part Of: Islets, 04 July 2014, Vol.6(4)
  • Identifier: ISSN: 1938-2014 ; E-ISSN: 1938-2022 ; DOI: 10.4161/19382014.2014.962386
  • Subjects: Chromanol 293b ; Gsis ; Glp-1 ; Islets of Langerhans ; Ipgtt ; Itt ; Kcnq1 ; Ogtt ; Anatomy & Physiology
  • Language: English

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