Genetic determinants of circulating GIP and GLP-1 concentrations

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Genetic determinants of circulating GIP and GLP-1 concentrations. / Almgren, Peter; Lindqvist, Andreas; Krus, Ulrika; Hakaste, Liisa; Ottosson-Laakso, Emilia; Asplund, Olof; Sonestedt, Emily; Prasad, Rashmi B; Laurila, Esa; Orho-Melander, Marju; Melander, Olle; Tuomi, Tiinamaija; Holst, Jens Juul; Nilsson, Peter M; Wierup, Nils; Groop, Leif; Ahlqvist, Emma.

In: JCI Insight, Vol. 2, No. 21, e93306, 02.11.2017.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Almgren, P, Lindqvist, A, Krus, U, Hakaste, L, Ottosson-Laakso, E, Asplund, O, Sonestedt, E, Prasad, RB, Laurila, E, Orho-Melander, M, Melander, O, Tuomi, T, Holst, JJ, Nilsson, PM, Wierup, N, Groop, L & Ahlqvist, E 2017, 'Genetic determinants of circulating GIP and GLP-1 concentrations', JCI Insight, vol. 2, no. 21, e93306. https://doi.org/10.1172/jci.insight.93306

APA

Almgren, P., Lindqvist, A., Krus, U., Hakaste, L., Ottosson-Laakso, E., Asplund, O., ... Ahlqvist, E. (2017). Genetic determinants of circulating GIP and GLP-1 concentrations. JCI Insight, 2(21), [e93306]. https://doi.org/10.1172/jci.insight.93306

Vancouver

Almgren P, Lindqvist A, Krus U, Hakaste L, Ottosson-Laakso E, Asplund O et al. Genetic determinants of circulating GIP and GLP-1 concentrations. JCI Insight. 2017 Nov 2;2(21). e93306. https://doi.org/10.1172/jci.insight.93306

Author

Almgren, Peter ; Lindqvist, Andreas ; Krus, Ulrika ; Hakaste, Liisa ; Ottosson-Laakso, Emilia ; Asplund, Olof ; Sonestedt, Emily ; Prasad, Rashmi B ; Laurila, Esa ; Orho-Melander, Marju ; Melander, Olle ; Tuomi, Tiinamaija ; Holst, Jens Juul ; Nilsson, Peter M ; Wierup, Nils ; Groop, Leif ; Ahlqvist, Emma. / Genetic determinants of circulating GIP and GLP-1 concentrations. In: JCI Insight. 2017 ; Vol. 2, No. 21.

Bibtex

@article{b0c80ccff30c4be69cac13565d52b28c,
title = "Genetic determinants of circulating GIP and GLP-1 concentrations",
abstract = "The secretion of insulin and glucagon from the pancreas and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) from the gastrointestinal tract is essential for glucose homeostasis. Several novel treatment strategies for type 2 diabetes (T2D) mimic GLP-1 actions or inhibit incretin degradation (DPP4 inhibitors), but none is thus far aimed at increasing the secretion of endogenous incretins. In order to identify new potential therapeutic targets for treatment of T2D, we performed a meta-analysis of a GWAS and an exome-wide association study of circulating insulin, glucagon, GIP, and GLP-1 concentrations measured during an oral glucose tolerance test in up to 7,828 individuals. We identified 6 genome-wide significant functional loci associated with plasma incretin concentrations in or near the SLC5A1 (encoding SGLT1), GIPR, ABO, GLP2R, F13A1, and HOXD1 genes and studied the effect of these variants on mRNA expression in pancreatic islet and on metabolic phenotypes. Immunohistochemistry showed expression of GIPR, ABO, and HOXD1 in human enteroendocrine cells and expression of ABO in pancreatic islets, supporting a role in hormone secretion. This study thus provides candidate genes and insight into mechanisms by which secretion and breakdown of GIP and GLP-1 are regulated.",
keywords = "Journal Article",
author = "Peter Almgren and Andreas Lindqvist and Ulrika Krus and Liisa Hakaste and Emilia Ottosson-Laakso and Olof Asplund and Emily Sonestedt and Prasad, {Rashmi B} and Esa Laurila and Marju Orho-Melander and Olle Melander and Tiinamaija Tuomi and Holst, {Jens Juul} and Nilsson, {Peter M} and Nils Wierup and Leif Groop and Emma Ahlqvist",
year = "2017",
month = "11",
day = "2",
doi = "10.1172/jci.insight.93306",
language = "English",
volume = "2",
journal = "JCI Insight",
issn = "2379-3708",
number = "21",

}

RIS

TY - JOUR

T1 - Genetic determinants of circulating GIP and GLP-1 concentrations

AU - Almgren, Peter

AU - Lindqvist, Andreas

AU - Krus, Ulrika

AU - Hakaste, Liisa

AU - Ottosson-Laakso, Emilia

AU - Asplund, Olof

AU - Sonestedt, Emily

AU - Prasad, Rashmi B

AU - Laurila, Esa

AU - Orho-Melander, Marju

AU - Melander, Olle

AU - Tuomi, Tiinamaija

AU - Holst, Jens Juul

AU - Nilsson, Peter M

AU - Wierup, Nils

AU - Groop, Leif

AU - Ahlqvist, Emma

PY - 2017/11/2

Y1 - 2017/11/2

N2 - The secretion of insulin and glucagon from the pancreas and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) from the gastrointestinal tract is essential for glucose homeostasis. Several novel treatment strategies for type 2 diabetes (T2D) mimic GLP-1 actions or inhibit incretin degradation (DPP4 inhibitors), but none is thus far aimed at increasing the secretion of endogenous incretins. In order to identify new potential therapeutic targets for treatment of T2D, we performed a meta-analysis of a GWAS and an exome-wide association study of circulating insulin, glucagon, GIP, and GLP-1 concentrations measured during an oral glucose tolerance test in up to 7,828 individuals. We identified 6 genome-wide significant functional loci associated with plasma incretin concentrations in or near the SLC5A1 (encoding SGLT1), GIPR, ABO, GLP2R, F13A1, and HOXD1 genes and studied the effect of these variants on mRNA expression in pancreatic islet and on metabolic phenotypes. Immunohistochemistry showed expression of GIPR, ABO, and HOXD1 in human enteroendocrine cells and expression of ABO in pancreatic islets, supporting a role in hormone secretion. This study thus provides candidate genes and insight into mechanisms by which secretion and breakdown of GIP and GLP-1 are regulated.

AB - The secretion of insulin and glucagon from the pancreas and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) from the gastrointestinal tract is essential for glucose homeostasis. Several novel treatment strategies for type 2 diabetes (T2D) mimic GLP-1 actions or inhibit incretin degradation (DPP4 inhibitors), but none is thus far aimed at increasing the secretion of endogenous incretins. In order to identify new potential therapeutic targets for treatment of T2D, we performed a meta-analysis of a GWAS and an exome-wide association study of circulating insulin, glucagon, GIP, and GLP-1 concentrations measured during an oral glucose tolerance test in up to 7,828 individuals. We identified 6 genome-wide significant functional loci associated with plasma incretin concentrations in or near the SLC5A1 (encoding SGLT1), GIPR, ABO, GLP2R, F13A1, and HOXD1 genes and studied the effect of these variants on mRNA expression in pancreatic islet and on metabolic phenotypes. Immunohistochemistry showed expression of GIPR, ABO, and HOXD1 in human enteroendocrine cells and expression of ABO in pancreatic islets, supporting a role in hormone secretion. This study thus provides candidate genes and insight into mechanisms by which secretion and breakdown of GIP and GLP-1 are regulated.

KW - Journal Article

U2 - 10.1172/jci.insight.93306

DO - 10.1172/jci.insight.93306

M3 - Journal article

VL - 2

JO - JCI Insight

JF - JCI Insight

SN - 2379-3708

IS - 21

M1 - e93306

ER -

ID: 189624585