Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets

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Standard

Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets. / Adriaenssens, Alice E; Svendsen, Berit; Lam, Brian Y H; Yeo, Giles S H; Holst, Jens J; Reimann, Frank; Gribble, Fiona M.

I: Diabetologia, Bind 59, Nr. 10, 10.2016, s. 2156-2165.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Adriaenssens, AE, Svendsen, B, Lam, BYH, Yeo, GSH, Holst, JJ, Reimann, F & Gribble, FM 2016, 'Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets', Diabetologia, bind 59, nr. 10, s. 2156-2165. https://doi.org/10.1007/s00125-016-4033-1

APA

Adriaenssens, A. E., Svendsen, B., Lam, B. Y. H., Yeo, G. S. H., Holst, J. J., Reimann, F., & Gribble, F. M. (2016). Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets. Diabetologia, 59(10), 2156-2165. https://doi.org/10.1007/s00125-016-4033-1

Vancouver

Adriaenssens AE, Svendsen B, Lam BYH, Yeo GSH, Holst JJ, Reimann F o.a. Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets. Diabetologia. 2016 okt;59(10):2156-2165. https://doi.org/10.1007/s00125-016-4033-1

Author

Adriaenssens, Alice E ; Svendsen, Berit ; Lam, Brian Y H ; Yeo, Giles S H ; Holst, Jens J ; Reimann, Frank ; Gribble, Fiona M. / Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets. I: Diabetologia. 2016 ; Bind 59, Nr. 10. s. 2156-2165.

Bibtex

@article{9a125a108f444938b9e453d09c997373,
title = "Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets",
abstract = "AIMS/HYPOTHESIS: Intra-islet and gut-islet crosstalk are critical in orchestrating basal and postprandial metabolism. The aim of this study was to identify regulatory proteins and receptors underlying somatostatin secretion though the use of transcriptomic comparison of purified murine alpha, beta and delta cells.METHODS: Sst-Cre mice crossed with fluorescent reporters were used to identify delta cells, while Glu-Venus (with Venus reported under the control of the Glu [also known as Gcg] promoter) mice were used to identify alpha and beta cells. Alpha, beta and delta cells were purified using flow cytometry and analysed by RNA sequencing. The role of the ghrelin receptor was validated by imaging delta cell calcium concentrations using islets with delta cell restricted expression of the calcium reporter GCaMP3, and in perfused mouse pancreases.RESULTS: A database was constructed of all genes expressed in alpha, beta and delta cells. The gene encoding the ghrelin receptor, Ghsr, was highlighted as being highly expressed and enriched in delta cells. Activation of the ghrelin receptor raised cytosolic calcium levels in primary pancreatic delta cells and enhanced somatostatin secretion in perfused pancreases, correlating with a decrease in insulin and glucagon release. The inhibition of insulin secretion by ghrelin was prevented by somatostatin receptor antagonism.CONCLUSIONS/INTERPRETATION: Our transcriptomic database of genes expressed in the principal islet cell populations will facilitate rational drug design to target specific islet cell types. The present study indicates that ghrelin acts specifically on delta cells within pancreatic islets to elicit somatostatin secretion, which in turn inhibits insulin and glucagon release. This highlights a potential role for ghrelin in the control of glucose metabolism.",
keywords = "Journal Article",
author = "Adriaenssens, {Alice E} and Berit Svendsen and Lam, {Brian Y H} and Yeo, {Giles S H} and Holst, {Jens J} and Frank Reimann and Gribble, {Fiona M}",
year = "2016",
month = "10",
doi = "10.1007/s00125-016-4033-1",
language = "English",
volume = "59",
pages = "2156--2165",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "10",

}

RIS

TY - JOUR

T1 - Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets

AU - Adriaenssens, Alice E

AU - Svendsen, Berit

AU - Lam, Brian Y H

AU - Yeo, Giles S H

AU - Holst, Jens J

AU - Reimann, Frank

AU - Gribble, Fiona M

PY - 2016/10

Y1 - 2016/10

N2 - AIMS/HYPOTHESIS: Intra-islet and gut-islet crosstalk are critical in orchestrating basal and postprandial metabolism. The aim of this study was to identify regulatory proteins and receptors underlying somatostatin secretion though the use of transcriptomic comparison of purified murine alpha, beta and delta cells.METHODS: Sst-Cre mice crossed with fluorescent reporters were used to identify delta cells, while Glu-Venus (with Venus reported under the control of the Glu [also known as Gcg] promoter) mice were used to identify alpha and beta cells. Alpha, beta and delta cells were purified using flow cytometry and analysed by RNA sequencing. The role of the ghrelin receptor was validated by imaging delta cell calcium concentrations using islets with delta cell restricted expression of the calcium reporter GCaMP3, and in perfused mouse pancreases.RESULTS: A database was constructed of all genes expressed in alpha, beta and delta cells. The gene encoding the ghrelin receptor, Ghsr, was highlighted as being highly expressed and enriched in delta cells. Activation of the ghrelin receptor raised cytosolic calcium levels in primary pancreatic delta cells and enhanced somatostatin secretion in perfused pancreases, correlating with a decrease in insulin and glucagon release. The inhibition of insulin secretion by ghrelin was prevented by somatostatin receptor antagonism.CONCLUSIONS/INTERPRETATION: Our transcriptomic database of genes expressed in the principal islet cell populations will facilitate rational drug design to target specific islet cell types. The present study indicates that ghrelin acts specifically on delta cells within pancreatic islets to elicit somatostatin secretion, which in turn inhibits insulin and glucagon release. This highlights a potential role for ghrelin in the control of glucose metabolism.

AB - AIMS/HYPOTHESIS: Intra-islet and gut-islet crosstalk are critical in orchestrating basal and postprandial metabolism. The aim of this study was to identify regulatory proteins and receptors underlying somatostatin secretion though the use of transcriptomic comparison of purified murine alpha, beta and delta cells.METHODS: Sst-Cre mice crossed with fluorescent reporters were used to identify delta cells, while Glu-Venus (with Venus reported under the control of the Glu [also known as Gcg] promoter) mice were used to identify alpha and beta cells. Alpha, beta and delta cells were purified using flow cytometry and analysed by RNA sequencing. The role of the ghrelin receptor was validated by imaging delta cell calcium concentrations using islets with delta cell restricted expression of the calcium reporter GCaMP3, and in perfused mouse pancreases.RESULTS: A database was constructed of all genes expressed in alpha, beta and delta cells. The gene encoding the ghrelin receptor, Ghsr, was highlighted as being highly expressed and enriched in delta cells. Activation of the ghrelin receptor raised cytosolic calcium levels in primary pancreatic delta cells and enhanced somatostatin secretion in perfused pancreases, correlating with a decrease in insulin and glucagon release. The inhibition of insulin secretion by ghrelin was prevented by somatostatin receptor antagonism.CONCLUSIONS/INTERPRETATION: Our transcriptomic database of genes expressed in the principal islet cell populations will facilitate rational drug design to target specific islet cell types. The present study indicates that ghrelin acts specifically on delta cells within pancreatic islets to elicit somatostatin secretion, which in turn inhibits insulin and glucagon release. This highlights a potential role for ghrelin in the control of glucose metabolism.

KW - Journal Article

U2 - 10.1007/s00125-016-4033-1

DO - 10.1007/s00125-016-4033-1

M3 - Journal article

VL - 59

SP - 2156

EP - 2165

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 10

ER -

ID: 166683349