Glucose-induced cAMP elevation in β-cells involves amplification of constitutive and glucagon-activated GLP-1 receptor signalling

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Sökning: WFRF:(Tengholm Anders) > (2020-2024) > Glucose-induced cAM...

Shuai, HongyanUppsala universitet,Institutionen för medicinsk cellbiologi,School of Basic Medicine Sciences, Dali University, Yunnan, China (författare)

Glucose-induced cAMP elevation in β-cells involves amplification of constitutive and glucagon-activated GLP-1 receptor signalling

Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

2021-01-09
John Wiley & Sons,2021
electronicrdacarrier

Nummerbeteckningar

LIBRIS-ID:oai:DiVA.org:uu-430557
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-430557URI
https://doi.org/10.1111/apha.13611DOI

Kompletterande språkuppgifter

Språk:engelska
Sammanfattning på:engelska

Ingår i deldatabas

SwePubSwePub

Klassifikation

Ämneskategori:ref swepub-contenttype
Ämneskategori:art swepub-publicationtype

Anmärkningar

AIM: cAMP typically signals downstream of Gs -coupled receptors and regulates numerous cell functions. In β-cells, cAMP amplifies Ca2+ -triggered exocytosis of insulin granules. Glucose-induced insulin secretion is associated with Ca2+ - and metabolism-dependent increases of the sub-plasma-membrane cAMP concentration ([cAMP]pm ) in β-cells, but potential links to canonical receptor signalling are unclear. The aim of this study was to clarify the role of glucagon-like peptide-1 receptors (GLP1Rs) for glucose-induced cAMP signalling in β-cells.METHODS: Total internal reflection microscopy and fluorescent reporters were used to monitor changes in cAMP, Ca2+ and ATP concentrations as well as insulin secretion in MIN6 cells and mouse and human β-cells. Insulin release from mouse and human islets was also measured with ELISA.RESULTS: The GLP1R antagonist exendin-(9-39) (ex-9) prevented both GLP1- and glucagon-induced elevations of [cAMP]pm , consistent with GLP1Rs being involved in the action of glucagon. This conclusion was supported by lack of unspecific effects of the antagonist in a reporter cell-line. Ex-9 also suppressed IBMX- and glucose-induced [cAMP]pm elevations. Depolarization with K+ triggered Ca2+ -dependent [cAMP]pm elevation, an effect that was amplified by high glucose. Ex-9 inhibited both the Ca2+ and glucose-metabolism-dependent actions on [cAMP]pm . The drug remained effective after minimizing paracrine signalling by dispersing the islets and it reduced basal [cAMP]pm in a cell-line heterologously expressing GLP1Rs, indicating that there is constitutive GLP1R signalling. The ex-9-induced reduction of [cAMP]pm in glucose-stimulated β-cells was paralleled by suppression of insulin secretion.CONCLUSION: Agonist-independent and glucagon-stimulated GLP1R signalling in β-cells contributes to basal and glucose-induced cAMP production and insulin secretion.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
adenylyl cyclase
exendin-(9-39)
glucagon
glucagon-like peptide-1
insulin secretion
pancreatic islets

Biuppslag (personer, institutioner, konferenser, titlar ...)

Xu, YunjianUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)yunxu459 (författare)
Ahooghalandari, ParvinUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)paaho498 (författare)
Tengholm, Anders,1971-Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)andeteng (författare)
Uppsala universitetInstitutionen för medicinsk cellbiologi (creator_code:org_t)

Sammanhörande titlar

Ingår i:Acta Physiologica: John Wiley & Sons231:41748-17081748-1716

Internetlänk

Hitta via bibliotek

Acta Physiologica (Sök värdpublikationen i LIBRIS)

Till lärosätets databas

Hitta mer i SwePub

Av författaren/redakt...: Shuai, Hongyan; Xu, Yunjian; Ahooghalandari, ...; Tengholm, Anders ...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Cell och molekyl ...

Artiklar i publikationen: Acta Physiologic ...

Av lärosätet: Uppsala universitet

Sök utanför SwePub

Sök vidare i:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se