Voltage-gated K+ channel KCNQ1 regulates insulin secretion in MIN6 β-cell line

Yamagata, Kazuya; Senokuchi, Takafumi; Lu, Mei-Hong; Takemoto, Makoto; Karim, Md. Fazlul; Go, Chisa; Sato, Yuzo; Hatta, Mitsutoki; Yoshizawa, Tatsuya; Araki, Eiichi; Miyazaki, Jun‐ichi; Song, Wen Jie

doi:10.1016/j.bbrc.2011.03.083

Cited by 73 publications

(78 citation statements)

References 25 publications

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“…6,14,28 In support of this assumption, KCNQ1 inhibition has been reported to result in broadened action potential and enhanced insulin secretion in clonal pancreatic b-cells. 14,15 Yet the regulation of insulin secretion is a multi-tiered process, occurring at the level of not only the single b-cell, but also the pancreatic islet, the whole pancreas, and the intact organism. 30 It is necessary to study the effect of KCNQ1 inhibition on insulin secretion at the level of primary islets as well as intact animals.…”

Section: Discussionmentioning

confidence: 87%

“…Chromanol 293B promotes insulin secretion from primary islets Chromanol 293B at 100 mM has been shown to enhance insulin secretion in insulinoma cell lines, 14,15 but the effect of this pharmacological tool on insulin secretion in primary islets has yet to be determined. As demonstrated in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…29 Thus, it seems plausible that enhanced KCNQ1 function is responsible for the development of T2D. 6,14,28 In support of this assumption, KCNQ1 inhibition has been reported to result in broadened action potential and enhanced insulin secretion in clonal pancreatic b-cells. 14,15 Yet the regulation of insulin secretion is a multi-tiered process, occurring at the level of not only the single b-cell, but also the pancreatic islet, the whole pancreas, and the intact organism.…”

Section: Discussionmentioning

confidence: 96%

“…13 In insulinoma cell lines, the blockade of the KCNQ1 channel promoted insulin secretion while the increased expression of KCNQ1 impaired insulin secretion. 14,15 All these data suggest a direct regulatory role of KCNQ1 in b-cell function. Yet insulin secretion is a multi-tiered process involving the integration of many factors, and KCNQ1 is widely expressed in a number of tissues throughout the body, it is worthful to investigate the effect of KCNQ1 inhibition on insulin secretion at the level of pancreatic islet and intact animal.…”

Section: Introductionmentioning

confidence: 89%

“…As KCNQ1 channel is blocked by chromanol 293B, 14,15,18,19 we then investigated the effects of chromanol 293B on insulin secretion in vitro and in vivo. Our work showed that KCNQ1 was expressed in insulin-positive b-cells in pancreatic islets and GLP-1-positive L-cells in intestinal crypt.…”

Section: Introductionmentioning

confidence: 99%

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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

Wang

et al. 2014

Islets

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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 b-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 b-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.

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Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Liu

Wang

et al. 2014

Islets

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Early‐onset type 2 diabetes is associated with genetic variants of β‐cell function in the Chinese Han population

Kong

Zhang

Hong

et al. 2019

Diabetes Metabolism Res

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Aims:To investigate the genetic factors contributing to early-onset type 2 diabetes (EOD) in the Chinese Hans populations. Materials and methods:For 2734 newly diagnosed type 2 diabetes patients and 4041 normal glycemic controls, 25 single nucleotide polymorphisms from 24 genomic loci linked to diabetes were successfully genotyped. Three genetic risk scores (GRSs) were constructed, including the weighted type 2 diabetes-related GRS (wT-GRS), the weighted β-cell function-related GRS (wB-GRS), and the weighted GRS constructed by risk alleles not related to β-cell function (wNB-GRS).For patients with diabetes, EOD, middle-age-onset type 2 diabetes (MOD), and late-onset type 2 diabetes (LOD) were defined by onset ages ≤40, 40 to 60, and ≥60 years, respectively.Results: From single marker analysis, different gene profiles were identified between EOD and LOD patients. EOD patients had greater wT-GRS and wB-GRS values than LOD patients. After adjustment for sex, elevated wT-GRS and wB-GRS values were significantly associated with an increased risk for EOD by 1.11-and 1.21-fold per allele (P = 1.69 × 10 −7 ; 6.07 × 10 −8 ). The wT-GRS and wNB-GRS were nominally related to an increased risk of LOD by 1.03-fold per allele (P = 1.03 × 10 −2 , 1.78 × 10 −2 ). In patients with diabetes, higher wT-GRS and wB-GRS were associated with younger onset age [wT-GRS: β (SE) = -0.0033(0.0016), P = 3.74 × 10 −2 ; wB-GRS: −0.0076(0.0028), 7.45 × 10 −3 ] and decreased insulinogenic index [wT-GRS: -0.0384(0.0098), 9.39 × 10 −5 ; wB-GRS: −0.0722(0.0176), 4.21 × 10 −5 ]. Conclusion:Our findings indicate a strong genetic predisposition for EOD, which can be mainly attributed to genetic variants linked to β-cell function, suggesting the β-cell dysfunction plays a key role in the pathogenesis of EOD in Chinese Han individuals.

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Stimulus-Secretion Coupling in Beta-Cells: From Basic to Bedside

Islam

2019

Advances in Experimental Medicine and Biology

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Voltage-gated K+ channel KCNQ1 regulates insulin secretion in MIN6 β-cell line

Cited by 73 publications

References 25 publications

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

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

Early‐onset type 2 diabetes is associated with genetic variants of β‐cell function in the Chinese Han population

Stimulus-Secretion Coupling in Beta-Cells: From Basic to Bedside

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