A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin

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A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. / Egerod, Kristoffer Lihme; Engelstoft, Maja Storm; Grunddal, Kaare Villum; Nøhr, Mark Klitgaard; Secher, Anna Elisabet Lilja; Sakata, Ichiro; Pedersen, Jens; Windeløv, Johanne A; Füchtbauer, Ernst-Martin; Olsen, Jørgen; Sundler, Frank; Christensen, Jan P; Wierup, Nils; Olsen, Jesper V; Holst, Jens Juul; Zigman, Jeffrey M; Poulsen, Steen S; Schwartz, Thue W.

I: Contemporary Endocrinology, Bind 153, Nr. 12, 2012, s. 5782-5795.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Egerod, KL, Engelstoft, MS, Grunddal, KV, Nøhr, MK, Secher, AEL, Sakata, I, Pedersen, J, Windeløv, JA, Füchtbauer, E-M, Olsen, J, Sundler, F, Christensen, JP, Wierup, N, Olsen, JV, Holst, JJ, Zigman, JM, Poulsen, SS & Schwartz, TW 2012, 'A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin', Contemporary Endocrinology, bind 153, nr. 12, s. 5782-5795. https://doi.org/10.1210/en.2012-1595

APA

Egerod, K. L., Engelstoft, M. S., Grunddal, K. V., Nøhr, M. K., Secher, A. E. L., Sakata, I., ... Schwartz, T. W. (2012). A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. Contemporary Endocrinology, 153(12), 5782-5795. https://doi.org/10.1210/en.2012-1595

CBE

Egerod KL, Engelstoft MS, Grunddal KV, Nøhr MK, Secher AEL, Sakata I, Pedersen J, Windeløv JA, Füchtbauer E-M, Olsen J, Sundler F, Christensen JP, Wierup N, Olsen JV, Holst JJ, Zigman JM, Poulsen SS, Schwartz TW. 2012. A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. Contemporary Endocrinology. 153(12):5782-5795. https://doi.org/10.1210/en.2012-1595

MLA

Vancouver

Egerod KL, Engelstoft MS, Grunddal KV, Nøhr MK, Secher AEL, Sakata I o.a. A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. Contemporary Endocrinology. 2012;153(12):5782-5795. https://doi.org/10.1210/en.2012-1595

Author

Egerod, Kristoffer Lihme ; Engelstoft, Maja Storm ; Grunddal, Kaare Villum ; Nøhr, Mark Klitgaard ; Secher, Anna Elisabet Lilja ; Sakata, Ichiro ; Pedersen, Jens ; Windeløv, Johanne A ; Füchtbauer, Ernst-Martin ; Olsen, Jørgen ; Sundler, Frank ; Christensen, Jan P ; Wierup, Nils ; Olsen, Jesper V ; Holst, Jens Juul ; Zigman, Jeffrey M ; Poulsen, Steen S ; Schwartz, Thue W. / A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. I: Contemporary Endocrinology. 2012 ; Bind 153, Nr. 12. s. 5782-5795.

Bibtex

@article{738fb8b364b0493e8a985ff40fadd57e,
title = "A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin",
abstract = "Enteroendocrine cells such as duodenal cholecystokinin (CCK cells) are generally thought to be confined to certain segments of the gastrointestinal (GI) tract and to store and release peptides derived from only a single peptide precursor. In the current study, however, transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the CCK promoter demonstrated a distribution pattern of CCK-eGFP positive cells that extended throughout the intestine. Quantitative PCR and liquid chromatography-mass spectrometry proteomic analyses of isolated, FACS-purified CCK-eGFP-positive cells demonstrated expression of not only CCK but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP), peptide YY (PYY), neurotensin, and secretin, but not somatostatin. Immunohistochemistry confirmed this expression pattern. The broad coexpression phenomenon was observed both in crypts and villi as demonstrated by immunohistochemistry and FACS analysis of separated cell populations. Single-cell quantitative PCR indicated that approximately half of the duodenal CCK-eGFP cells express one peptide precursor in addition to CCK, whereas an additional smaller fraction expresses two peptide precursors in addition to CCK. The coexpression pattern was further confirmed through a cell ablation study based on expression of the human diphtheria toxin receptor under the control of the proglucagon promoter, in which activation of the receptor resulted in a marked reduction not only in GLP-1 cells, but also PYY, neurotensin, GIP, CCK, and secretin cells, whereas somatostatin cells were spared. Key elements of the coexpression pattern were confirmed by immunohistochemical double staining in human small intestine. It is concluded that a lineage of mature enteroendocrine cells have the ability to coexpress members of a group of functionally related peptides: CCK, secretin, GIP, GLP-1, PYY, and neurotensin, suggesting a potential therapeutic target for the treatment and prevention of diabetes and obesity.",
keywords = "Animals, Cell Lineage, Cell Separation, Cholecystokinin, Diabetes Mellitus, Enteroendocrine Cells, Flow Cytometry, Gastric Inhibitory Polypeptide, Gene Expression Regulation, Ghrelin, Glucagon-Like Peptide 1, Green Fluorescent Proteins, Humans, Immunohistochemistry, Intestines, Mice, Mice, Transgenic, Neurotensin, Obesity, Peptide YY, Promoter Regions, Genetic",
author = "Egerod, {Kristoffer Lihme} and Engelstoft, {Maja Storm} and Grunddal, {Kaare Villum} and N{\o}hr, {Mark Klitgaard} and Secher, {Anna Elisabet Lilja} and Ichiro Sakata and Jens Pedersen and Windel{\o}v, {Johanne A} and Ernst-Martin F{\"u}chtbauer and J{\o}rgen Olsen and Frank Sundler and Christensen, {Jan P} and Nils Wierup and Olsen, {Jesper V} and Holst, {Jens Juul} and Zigman, {Jeffrey M} and Poulsen, {Steen S} and Schwartz, {Thue W.}",
year = "2012",
doi = "10.1210/en.2012-1595",
language = "English",
volume = "153",
pages = "5782--5795",
journal = "Contemporary Endocrinology",
issn = "0196-8653",
publisher = "Humana Press, Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin

AU - Egerod, Kristoffer Lihme

AU - Engelstoft, Maja Storm

AU - Grunddal, Kaare Villum

AU - Nøhr, Mark Klitgaard

AU - Secher, Anna Elisabet Lilja

AU - Sakata, Ichiro

AU - Pedersen, Jens

AU - Windeløv, Johanne A

AU - Füchtbauer, Ernst-Martin

AU - Olsen, Jørgen

AU - Sundler, Frank

AU - Christensen, Jan P

AU - Wierup, Nils

AU - Olsen, Jesper V

AU - Holst, Jens Juul

AU - Zigman, Jeffrey M

AU - Poulsen, Steen S

AU - Schwartz, Thue W.

PY - 2012

Y1 - 2012

N2 - Enteroendocrine cells such as duodenal cholecystokinin (CCK cells) are generally thought to be confined to certain segments of the gastrointestinal (GI) tract and to store and release peptides derived from only a single peptide precursor. In the current study, however, transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the CCK promoter demonstrated a distribution pattern of CCK-eGFP positive cells that extended throughout the intestine. Quantitative PCR and liquid chromatography-mass spectrometry proteomic analyses of isolated, FACS-purified CCK-eGFP-positive cells demonstrated expression of not only CCK but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP), peptide YY (PYY), neurotensin, and secretin, but not somatostatin. Immunohistochemistry confirmed this expression pattern. The broad coexpression phenomenon was observed both in crypts and villi as demonstrated by immunohistochemistry and FACS analysis of separated cell populations. Single-cell quantitative PCR indicated that approximately half of the duodenal CCK-eGFP cells express one peptide precursor in addition to CCK, whereas an additional smaller fraction expresses two peptide precursors in addition to CCK. The coexpression pattern was further confirmed through a cell ablation study based on expression of the human diphtheria toxin receptor under the control of the proglucagon promoter, in which activation of the receptor resulted in a marked reduction not only in GLP-1 cells, but also PYY, neurotensin, GIP, CCK, and secretin cells, whereas somatostatin cells were spared. Key elements of the coexpression pattern were confirmed by immunohistochemical double staining in human small intestine. It is concluded that a lineage of mature enteroendocrine cells have the ability to coexpress members of a group of functionally related peptides: CCK, secretin, GIP, GLP-1, PYY, and neurotensin, suggesting a potential therapeutic target for the treatment and prevention of diabetes and obesity.

AB - Enteroendocrine cells such as duodenal cholecystokinin (CCK cells) are generally thought to be confined to certain segments of the gastrointestinal (GI) tract and to store and release peptides derived from only a single peptide precursor. In the current study, however, transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the CCK promoter demonstrated a distribution pattern of CCK-eGFP positive cells that extended throughout the intestine. Quantitative PCR and liquid chromatography-mass spectrometry proteomic analyses of isolated, FACS-purified CCK-eGFP-positive cells demonstrated expression of not only CCK but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP), peptide YY (PYY), neurotensin, and secretin, but not somatostatin. Immunohistochemistry confirmed this expression pattern. The broad coexpression phenomenon was observed both in crypts and villi as demonstrated by immunohistochemistry and FACS analysis of separated cell populations. Single-cell quantitative PCR indicated that approximately half of the duodenal CCK-eGFP cells express one peptide precursor in addition to CCK, whereas an additional smaller fraction expresses two peptide precursors in addition to CCK. The coexpression pattern was further confirmed through a cell ablation study based on expression of the human diphtheria toxin receptor under the control of the proglucagon promoter, in which activation of the receptor resulted in a marked reduction not only in GLP-1 cells, but also PYY, neurotensin, GIP, CCK, and secretin cells, whereas somatostatin cells were spared. Key elements of the coexpression pattern were confirmed by immunohistochemical double staining in human small intestine. It is concluded that a lineage of mature enteroendocrine cells have the ability to coexpress members of a group of functionally related peptides: CCK, secretin, GIP, GLP-1, PYY, and neurotensin, suggesting a potential therapeutic target for the treatment and prevention of diabetes and obesity.

KW - Animals

KW - Cell Lineage

KW - Cell Separation

KW - Cholecystokinin

KW - Diabetes Mellitus

KW - Enteroendocrine Cells

KW - Flow Cytometry

KW - Gastric Inhibitory Polypeptide

KW - Gene Expression Regulation

KW - Ghrelin

KW - Glucagon-Like Peptide 1

KW - Green Fluorescent Proteins

KW - Humans

KW - Immunohistochemistry

KW - Intestines

KW - Mice

KW - Mice, Transgenic

KW - Neurotensin

KW - Obesity

KW - Peptide YY

KW - Promoter Regions, Genetic

U2 - 10.1210/en.2012-1595

DO - 10.1210/en.2012-1595

M3 - Journal article

C2 - 23064014

VL - 153

SP - 5782

EP - 5795

JO - Contemporary Endocrinology

JF - Contemporary Endocrinology

SN - 0196-8653

IS - 12

ER -