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Optogenetic regulation of insulin secretion in pancreatic β-cells
Pancreatic β-cell insulin production is orchestrated by a complex circuitry involving intracellular elements including cyclic AMP (cAMP). Tackling aberrations in glucose-stimulated insulin release such as in diabetes with pharmacological agents, which boost the secretory capacity of β-cells, is link...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571193/ https://www.ncbi.nlm.nih.gov/pubmed/28839233 http://dx.doi.org/10.1038/s41598-017-09937-0 |
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author | Zhang, Fan Tzanakakis, Emmanuel S. |
author_facet | Zhang, Fan Tzanakakis, Emmanuel S. |
author_sort | Zhang, Fan |
collection | PubMed |
description | Pancreatic β-cell insulin production is orchestrated by a complex circuitry involving intracellular elements including cyclic AMP (cAMP). Tackling aberrations in glucose-stimulated insulin release such as in diabetes with pharmacological agents, which boost the secretory capacity of β-cells, is linked to adverse side effects. We hypothesized that a photoactivatable adenylyl cyclase (PAC) can be employed to modulate cAMP in β-cells with light thereby enhancing insulin secretion. To that end, the PAC gene from Beggiatoa (bPAC) was delivered to β-cells. A cAMP increase was noted within 5 minutes of photostimulation and a significant drop at 12 minutes post-illumination. The concomitant augmented insulin secretion was comparable to that from β-cells treated with secretagogues. Greater insulin release was also observed over repeated cycles of photoinduction without adverse effects on viability and proliferation. Furthermore, the expression and activation of bPAC increased cAMP and insulin secretion in murine islets and in β-cell pseudoislets, which displayed a more pronounced light-triggered hormone secretion compared to that of β-cell monolayers. Calcium channel blocking curtailed the enhanced insulin response due to bPAC activity. This optogenetic system with modulation of cAMP and insulin release can be employed for the study of β-cell function and for enabling new therapeutic modalities for diabetes. |
format | Online Article Text |
id | pubmed-5571193 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55711932017-09-01 Optogenetic regulation of insulin secretion in pancreatic β-cells Zhang, Fan Tzanakakis, Emmanuel S. Sci Rep Article Pancreatic β-cell insulin production is orchestrated by a complex circuitry involving intracellular elements including cyclic AMP (cAMP). Tackling aberrations in glucose-stimulated insulin release such as in diabetes with pharmacological agents, which boost the secretory capacity of β-cells, is linked to adverse side effects. We hypothesized that a photoactivatable adenylyl cyclase (PAC) can be employed to modulate cAMP in β-cells with light thereby enhancing insulin secretion. To that end, the PAC gene from Beggiatoa (bPAC) was delivered to β-cells. A cAMP increase was noted within 5 minutes of photostimulation and a significant drop at 12 minutes post-illumination. The concomitant augmented insulin secretion was comparable to that from β-cells treated with secretagogues. Greater insulin release was also observed over repeated cycles of photoinduction without adverse effects on viability and proliferation. Furthermore, the expression and activation of bPAC increased cAMP and insulin secretion in murine islets and in β-cell pseudoislets, which displayed a more pronounced light-triggered hormone secretion compared to that of β-cell monolayers. Calcium channel blocking curtailed the enhanced insulin response due to bPAC activity. This optogenetic system with modulation of cAMP and insulin release can be employed for the study of β-cell function and for enabling new therapeutic modalities for diabetes. Nature Publishing Group UK 2017-08-24 /pmc/articles/PMC5571193/ /pubmed/28839233 http://dx.doi.org/10.1038/s41598-017-09937-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhang, Fan Tzanakakis, Emmanuel S. Optogenetic regulation of insulin secretion in pancreatic β-cells |
title | Optogenetic regulation of insulin secretion in pancreatic β-cells |
title_full | Optogenetic regulation of insulin secretion in pancreatic β-cells |
title_fullStr | Optogenetic regulation of insulin secretion in pancreatic β-cells |
title_full_unstemmed | Optogenetic regulation of insulin secretion in pancreatic β-cells |
title_short | Optogenetic regulation of insulin secretion in pancreatic β-cells |
title_sort | optogenetic regulation of insulin secretion in pancreatic β-cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571193/ https://www.ncbi.nlm.nih.gov/pubmed/28839233 http://dx.doi.org/10.1038/s41598-017-09937-0 |
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