2022
DOI: 10.1016/j.jbc.2021.101484
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Intra-islet glucagon confers β-cell glucose competence for first-phase insulin secretion and favors GLP-1R stimulation by exogenous glucagon

Abstract: This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, a… Show more

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Cited by 26 publications
(24 citation statements)
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“…Intriguingly, it is now understood that islet alpha cells secrete not only glucagon, but also GLP‐1 under conditions of stress, as might occur in db/db mice 21 . Because glucagon and GLP‐1 are both beta cell GLP‐1R agonists, 22,23 they might act as intra‐islet paracrine hormones to mediate the insulin secretagogue and blood glucose‐lowering actions of GTS‐21.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Intriguingly, it is now understood that islet alpha cells secrete not only glucagon, but also GLP‐1 under conditions of stress, as might occur in db/db mice 21 . Because glucagon and GLP‐1 are both beta cell GLP‐1R agonists, 22,23 they might act as intra‐islet paracrine hormones to mediate the insulin secretagogue and blood glucose‐lowering actions of GTS‐21.…”
Section: Discussionmentioning
confidence: 99%
“…Intriguingly, it is now understood that islet alpha cells secrete not only glucagon, but also GLP-1 under conditions of stress, as might occur in db/db mice. 21 Because glucagon and GLP-1 are both beta cell GLP-1R agonists, 22,23 they might act as intra-islet paracrine hormones to mediate the insulin secretagogue and blood glucose-lowering actions of GTS-21. Another possible explanation for the findings reported here is that GTS-21 acts at L cells to stimulate GLP-1 release, whereafter GLP-1 stimulates the GLP-1R on sensory vagus neurons located in close proximity to L cells in the intestinal wall.…”
Section: Discussionmentioning
confidence: 99%
“…GLUT1 expression decreased in Gcgr –/– mice but increased in wild-type mice after glucose stimulation ( 36 ). As a paracrine hormone, glucagon binds to GCGR with high affinity, while also exerting a “spillover” effect by binding to GLP-1R with low affinity ( 37 ). After glucagon binds to GCGR and GLP-1R on β cells, the activated receptors engage the G protein Gαs, which stimulate the generation of cyclic adenosine monophosphate (cAMP) ( 34 , 38 – 40 ).…”
Section: Mechanism By Which Glucagon Affects Insulin Secretionmentioning
confidence: 99%
“…The findings reported by Cabrera et al . 5 provide a theoretical rationale to support a possibility that dual agonist peptides, which simultaneously stimulate the GLP‐1R and GcgR, functionally restore the deranged GSIS in the diabetic condition. Based on this rationale, the mechanistic schema of GSIS in response to various stimulations, such as glucose alone, exogenous glucagon and exogenous GLP‐1, is shown in Figure 1 .…”
mentioning
confidence: 98%
“…Recently, Cabrera et al . 5 integrated understanding of GSIS by examining in more detail the effects of endogenous glucagon, extrinsic glucagon, α‐cells to β‐cells communication, various receptors expressed on β‐cells and cAMP production involved in insulin secretion. They showed GSIS in the following three conditions using rat islets.…”
mentioning
confidence: 99%