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Glucose and GLP-1 Stimulate cAMP Production via Distinct Adenylyl Cyclases in INS-1E Insulinoma Cells

In β cells, both glucose and hormones, such as GLP-1, stimulate production of the second messenger cAMP, but glucose and GLP-1 elicit distinct cellular responses. We now show in INS-1E insulinoma cells that glucose and GLP-1 produce cAMP with distinct kinetics via different adenylyl cyclases. GLP-1...

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Autores principales: Ramos, Lavoisier S., Zippin, Jonathan Hale, Kamenetsky, Margarita, Buck, Jochen, Levin, Lonny R.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518727/
https://www.ncbi.nlm.nih.gov/pubmed/18695009
http://dx.doi.org/10.1085/jgp.200810044
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author Ramos, Lavoisier S.
Zippin, Jonathan Hale
Kamenetsky, Margarita
Buck, Jochen
Levin, Lonny R.
author_facet Ramos, Lavoisier S.
Zippin, Jonathan Hale
Kamenetsky, Margarita
Buck, Jochen
Levin, Lonny R.
author_sort Ramos, Lavoisier S.
collection PubMed
description In β cells, both glucose and hormones, such as GLP-1, stimulate production of the second messenger cAMP, but glucose and GLP-1 elicit distinct cellular responses. We now show in INS-1E insulinoma cells that glucose and GLP-1 produce cAMP with distinct kinetics via different adenylyl cyclases. GLP-1 induces a rapid cAMP signal mediated by G protein–responsive transmembrane adenylyl cyclases (tmAC). In contrast, glucose elicits a delayed cAMP rise mediated by bicarbonate, calcium, and ATP-sensitive soluble adenylyl cyclase (sAC). This glucose-induced, sAC-dependent cAMP rise is dependent upon calcium influx and is responsible for the glucose-induced activation of the mitogen-activated protein kinase (ERK1/2) pathway. These results demonstrate that sAC-generated and tmAC-generated cAMP define distinct signaling cascades.
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spelling pubmed-25187272009-03-01 Glucose and GLP-1 Stimulate cAMP Production via Distinct Adenylyl Cyclases in INS-1E Insulinoma Cells Ramos, Lavoisier S. Zippin, Jonathan Hale Kamenetsky, Margarita Buck, Jochen Levin, Lonny R. J Gen Physiol Articles In β cells, both glucose and hormones, such as GLP-1, stimulate production of the second messenger cAMP, but glucose and GLP-1 elicit distinct cellular responses. We now show in INS-1E insulinoma cells that glucose and GLP-1 produce cAMP with distinct kinetics via different adenylyl cyclases. GLP-1 induces a rapid cAMP signal mediated by G protein–responsive transmembrane adenylyl cyclases (tmAC). In contrast, glucose elicits a delayed cAMP rise mediated by bicarbonate, calcium, and ATP-sensitive soluble adenylyl cyclase (sAC). This glucose-induced, sAC-dependent cAMP rise is dependent upon calcium influx and is responsible for the glucose-induced activation of the mitogen-activated protein kinase (ERK1/2) pathway. These results demonstrate that sAC-generated and tmAC-generated cAMP define distinct signaling cascades. The Rockefeller University Press 2008-09 /pmc/articles/PMC2518727/ /pubmed/18695009 http://dx.doi.org/10.1085/jgp.200810044 Text en © 2008 Ramos et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jgp.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Articles
Ramos, Lavoisier S.
Zippin, Jonathan Hale
Kamenetsky, Margarita
Buck, Jochen
Levin, Lonny R.
Glucose and GLP-1 Stimulate cAMP Production via Distinct Adenylyl Cyclases in INS-1E Insulinoma Cells
title Glucose and GLP-1 Stimulate cAMP Production via Distinct Adenylyl Cyclases in INS-1E Insulinoma Cells
title_full Glucose and GLP-1 Stimulate cAMP Production via Distinct Adenylyl Cyclases in INS-1E Insulinoma Cells
title_fullStr Glucose and GLP-1 Stimulate cAMP Production via Distinct Adenylyl Cyclases in INS-1E Insulinoma Cells
title_full_unstemmed Glucose and GLP-1 Stimulate cAMP Production via Distinct Adenylyl Cyclases in INS-1E Insulinoma Cells
title_short Glucose and GLP-1 Stimulate cAMP Production via Distinct Adenylyl Cyclases in INS-1E Insulinoma Cells
title_sort glucose and glp-1 stimulate camp production via distinct adenylyl cyclases in ins-1e insulinoma cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518727/
https://www.ncbi.nlm.nih.gov/pubmed/18695009
http://dx.doi.org/10.1085/jgp.200810044
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