Electrical activity‐triggered glucagon‐like peptide‐1 secretion from primary murine L‐cells

Rogers, Gareth J.; Tolhurst, Gwen; Ramzan, Amin; Habib, Abdella M.; Parker, Helen; Gribble, Fiona M.; Reimann, Frank

doi:10.1113/jphysiol.2010.198069

Cited by 74 publications

(109 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In intestine (Fig. 1G-L), consistent with previous work, 21,22 KCNQ1 immunoreactivity was observed in basolateral membranes of crypt epithelial cells. Although we did not find colocalization of KCNQ1 and GLP-1 in intestinal villi, KCNQ1 was detected in the GLP-1 positive cell in intestinal crypt.…”

Section: Resultssupporting

confidence: 80%

“…16 In line with their assumption, the KCNQ1 was then be found by RT-PCR to be the most highly expressed K C channel gene-family member in L-cells. 21 Here by double-immunofluorescence staining, KCNQ1 was found to be expressed in GLP-1-positive L-cells in intestinal crypt but not in intestinal villi. This result is partly agree with the previous report that chromanol sensitive K C current in crypts was larger than villi.…”

Section: Discussionmentioning

confidence: 99%

“…As the expression of KCNQ1 is relatively higher in crypt, it seems also reasonable that the KCNQ1 might influence incretin level indirectly by altering crypt function or L-cells number. 21 Nevertheless, it should be noted that the changes of GLP-1 during OGTT we observed in 293B-mice might just be a part of scenario. The immunofluorescence in pancreas indicates that KCNQ1 stains not only insulin positive but also some insulin negative cells of islet.…”

Section: 22mentioning

confidence: 99%

See 2 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

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: 22mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…In our study of carriers of functional KCNQ1 mutations, we do not find any difference in circulating incretin levels between patients and control individuals. This is in agreement with recent studies of L cells (45) and recent human genetic studies (46), indicating that KCNQ1 does not have a major influence on incretin secretion.…”

supporting

confidence: 93%

KCNQ1 Long QT Syndrome Patients Have Hyperinsulinemia and Symptomatic Hypoglycemia

et al. 2014

View full text Add to dashboard Cite

Patients with loss-of-function mutations in KCNQ1 have KCNQ1 long QT syndrome (LQTS). KCNQ1 encodes a voltage-gated K + channel located in both cardiomyocytes and pancreatic b-cells. Inhibition of KCNQ1 in b-cells increases insulin secretion. Therefore KCNQ1 LQTS patients may exhibit increased insulin secretion. Fourteen patients, from six families, diagnosed with KCNQ1 LQTS were individually matched to two randomly chosen BMI-, age-, and sex-matched control participants and underwent an oral glucose tolerance test (OGTT), a hypoglycemia questionnaire, and continuous glucose monitoring. KCNQ1 mutation carriers showed increased insulin release (area under the curve 45.6 6 6.3 vs. 26.0 6 2.8 min $ nmol/L insulin) and b-cell glucose sensitivity and had lower levels of plasma glucose and serum potassium upon oral glucose stimulation and increased hypoglycemic symptoms. Prolonged OGTT in four available patients and matched control subjects revealed hypoglycemia in carriers after 210 min (range 1.4-3.6 vs. 4.1-5.3 mmol/L glucose), and 24-h glucose profiles showed that the patients spent 77 6 18 min per 24 h in hypoglycemic states (<3.9 mmol/L glucose) with 36 6 10 min (<2.8 mmol/L glucose) vs. 0 min (<3.9 mmol/L glucose) for the control participants. The phenotype of patients with KCNQ1 LQTS, caused by mutations in KCNQ1, includes, besides long QT, hyperinsulinemia, clinically relevant symptomatic reactive hypoglycemia, and low potassium after an oral glucose challenge, suggesting that KCNQ1 mutations may explain some cases of "essential" reactive hypoglycemia.

show abstract

“…The circuit is complex but begins at the wall of the intestine where nutrients come into contact with sensory epithelial cells, called enteroendocrine cells. Unlike other sensory epithelial cells, such as taste cells, enteroendocrine cells are dispersed throughout the gut epithelium at a ratio of one to one thousand [4][5][6][7] . Consequently, they have been difficult to identify and study, and for long time they were viewed only as a source of gut hormones.…”

Section: Introductionmentioning

confidence: 99%

Correlative Confocal and 3D Electron Microscopy of a Specific Sensory Cell

Bohórquez

Haque

Medicetty

et al. 2015

JoVE

View full text Add to dashboard Cite

Delineation of a cell's ultrastructure is important for understanding its function. This can be a daunting project for rare cell types diffused throughout tissues made of diverse cell types, such as enteroendocrine cells of the intestinal epithelium. These gastrointestinal sensors of food and bacteria have been difficult to study because they are dispersed among other epithelial cells at a ratio of 1:1,000. Recently, transgenic reporter mice have been generated to identify enteroendocrine cells by means of fluorescence. One of those is the peptide YY-GFP mouse. Using this mouse, we developed a method to correlate confocal and serial block-face scanning electron microscopy. We named the method cocem3D and applied it to identify a specific enteroendocrine cell in tissue and unveil the cell's ultrastructure in 3D. The resolution of cocem3D is sufficient to identify organelles as small as secretory vesicles and to distinguish cell membranes for volume rendering. Cocem3D can be easily adapted to study the 3D ultrastructure of other specific cell types in their native tissue.

show abstract

Electrical activity‐triggered glucagon‐like peptide‐1 secretion from primary murine L‐cells

Cited by 74 publications

References 27 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

KCNQ1 Long QT Syndrome Patients Have Hyperinsulinemia and Symptomatic Hypoglycemia

Correlative Confocal and 3D Electron Microscopy of a Specific Sensory Cell

Contact Info

Product

Resources

About