Pdx1- and Ngn3-cre-mediated PLAG1 expression in the pancreas leads to endocrine hormone imbalances that affect glucose metabolism

Jeroen Declercq, Anujith Kumar, Conny Gysemans, Caterina di Pietro, Anica Schraenen, Marie Chintinne, Katleen Lemaire, Leentje van Lomme, M. van De Casteele, Harry Heimberg, Daniel Pipeleers, Frans C. Schuit, Chantal Mathieu, Nadine Ectors, Wim J M van de ven, Catherine M. Verfaillie

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Pleomorphic adenoma gene-like 1 (PLAGL1) has been linked to transient neonatal diabetes mellitus. Here, we investigated the role of the related pleomorphic adenoma gene 1 (PLAG1) in glucose homeostasis. PLAG1 transgenic mice in which expression of the PLAG1 transgene can be targeted to different organs by Cre-mediated modulation were crossed with Pdx1-Cre or Ngn3-Cre mice, resulting in double transgenic P1- Pdx1Cre or P1-Ngn3Cre mice, respectively. P1-Pdx1Cre and P1-Ngn3Cre mice developed hyperplasia of pancreatic islets due to increased β- and δ- but not α-cell proliferation. In young P1-Pdx1Cre mice (less than 15 weeks) there was a balanced increase in the pancreatic content of insulin and somatostatin, which was associated with normoglycemia. In older P1-Pdx1Cre mice the pancreatic somatostatin content far exceeded that of insulin, leading to the progressive development of severe hypoglycemia beyond 30 weeks. In contrast, in older P1-Ngn3Cre mice the relative increase of the pancreatic insulin content exceeded that of somatostatin and these mice remained normoglycemic. In conclusion, forced expression of PLAG1 under the control of the Pdx1 or Ngn3 promoter in murine pancreas induces different degrees of endocrine hormone imbalances within the pancreas, which is associated with hypoglycemia in P1-Pdx1Cre mice but not P1-Ngn3Cre mice. These results suggest that once stem cell-derived islet transplantations become possible, the appropriate balance between different hormone-producing cells will need to be preserved to prevent deregulated glucose metabolism.

Original languageEnglish
Pages (from-to)1285-1297
Number of pages13
JournalCell Transplantation
Volume20
Issue number8
DOIs
Publication statusPublished - 2011

Fingerprint

Pleomorphic Adenoma
Hormones
Metabolism
Glucose
Pancreas
Genes
Insulin
Gene Expression
Somatostatin
Cell proliferation
Hypoglycemia
Medical problems
Stem cells
Modulation
Islets of Langerhans Transplantation
Transgenes
Islets of Langerhans
Transgenic Mice
Hyperplasia
Diabetes Mellitus

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Declercq, Jeroen ; Kumar, Anujith ; Gysemans, Conny ; di Pietro, Caterina ; Schraenen, Anica ; Chintinne, Marie ; Lemaire, Katleen ; van Lomme, Leentje ; van De Casteele, M. ; Heimberg, Harry ; Pipeleers, Daniel ; Schuit, Frans C. ; Mathieu, Chantal ; Ectors, Nadine ; van de ven, Wim J M ; Verfaillie, Catherine M. / Pdx1- and Ngn3-cre-mediated PLAG1 expression in the pancreas leads to endocrine hormone imbalances that affect glucose metabolism. In: Cell Transplantation. 2011 ; Vol. 20, No. 8. pp. 1285-1297.
@article{874ec30be9c54db28edc0f5b70b13bfd,
title = "Pdx1- and Ngn3-cre-mediated PLAG1 expression in the pancreas leads to endocrine hormone imbalances that affect glucose metabolism",
abstract = "Pleomorphic adenoma gene-like 1 (PLAGL1) has been linked to transient neonatal diabetes mellitus. Here, we investigated the role of the related pleomorphic adenoma gene 1 (PLAG1) in glucose homeostasis. PLAG1 transgenic mice in which expression of the PLAG1 transgene can be targeted to different organs by Cre-mediated modulation were crossed with Pdx1-Cre or Ngn3-Cre mice, resulting in double transgenic P1- Pdx1Cre or P1-Ngn3Cre mice, respectively. P1-Pdx1Cre and P1-Ngn3Cre mice developed hyperplasia of pancreatic islets due to increased β- and δ- but not α-cell proliferation. In young P1-Pdx1Cre mice (less than 15 weeks) there was a balanced increase in the pancreatic content of insulin and somatostatin, which was associated with normoglycemia. In older P1-Pdx1Cre mice the pancreatic somatostatin content far exceeded that of insulin, leading to the progressive development of severe hypoglycemia beyond 30 weeks. In contrast, in older P1-Ngn3Cre mice the relative increase of the pancreatic insulin content exceeded that of somatostatin and these mice remained normoglycemic. In conclusion, forced expression of PLAG1 under the control of the Pdx1 or Ngn3 promoter in murine pancreas induces different degrees of endocrine hormone imbalances within the pancreas, which is associated with hypoglycemia in P1-Pdx1Cre mice but not P1-Ngn3Cre mice. These results suggest that once stem cell-derived islet transplantations become possible, the appropriate balance between different hormone-producing cells will need to be preserved to prevent deregulated glucose metabolism.",
author = "Jeroen Declercq and Anujith Kumar and Conny Gysemans and {di Pietro}, Caterina and Anica Schraenen and Marie Chintinne and Katleen Lemaire and {van Lomme}, Leentje and {van De Casteele}, M. and Harry Heimberg and Daniel Pipeleers and Schuit, {Frans C.} and Chantal Mathieu and Nadine Ectors and {van de ven}, {Wim J M} and Verfaillie, {Catherine M.}",
year = "2011",
doi = "10.3727/096368910X550242",
language = "English",
volume = "20",
pages = "1285--1297",
journal = "Cell Transplantation",
issn = "0963-6897",
publisher = "Cognizant Communication Corporation",
number = "8",

}

Declercq, J, Kumar, A, Gysemans, C, di Pietro, C, Schraenen, A, Chintinne, M, Lemaire, K, van Lomme, L, van De Casteele, M, Heimberg, H, Pipeleers, D, Schuit, FC, Mathieu, C, Ectors, N, van de ven, WJM & Verfaillie, CM 2011, 'Pdx1- and Ngn3-cre-mediated PLAG1 expression in the pancreas leads to endocrine hormone imbalances that affect glucose metabolism', Cell Transplantation, vol. 20, no. 8, pp. 1285-1297. https://doi.org/10.3727/096368910X550242

Pdx1- and Ngn3-cre-mediated PLAG1 expression in the pancreas leads to endocrine hormone imbalances that affect glucose metabolism. / Declercq, Jeroen; Kumar, Anujith; Gysemans, Conny; di Pietro, Caterina; Schraenen, Anica; Chintinne, Marie; Lemaire, Katleen; van Lomme, Leentje; van De Casteele, M.; Heimberg, Harry; Pipeleers, Daniel; Schuit, Frans C.; Mathieu, Chantal; Ectors, Nadine; van de ven, Wim J M; Verfaillie, Catherine M.

In: Cell Transplantation, Vol. 20, No. 8, 2011, p. 1285-1297.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pdx1- and Ngn3-cre-mediated PLAG1 expression in the pancreas leads to endocrine hormone imbalances that affect glucose metabolism

AU - Declercq, Jeroen

AU - Kumar, Anujith

AU - Gysemans, Conny

AU - di Pietro, Caterina

AU - Schraenen, Anica

AU - Chintinne, Marie

AU - Lemaire, Katleen

AU - van Lomme, Leentje

AU - van De Casteele, M.

AU - Heimberg, Harry

AU - Pipeleers, Daniel

AU - Schuit, Frans C.

AU - Mathieu, Chantal

AU - Ectors, Nadine

AU - van de ven, Wim J M

AU - Verfaillie, Catherine M.

PY - 2011

Y1 - 2011

N2 - Pleomorphic adenoma gene-like 1 (PLAGL1) has been linked to transient neonatal diabetes mellitus. Here, we investigated the role of the related pleomorphic adenoma gene 1 (PLAG1) in glucose homeostasis. PLAG1 transgenic mice in which expression of the PLAG1 transgene can be targeted to different organs by Cre-mediated modulation were crossed with Pdx1-Cre or Ngn3-Cre mice, resulting in double transgenic P1- Pdx1Cre or P1-Ngn3Cre mice, respectively. P1-Pdx1Cre and P1-Ngn3Cre mice developed hyperplasia of pancreatic islets due to increased β- and δ- but not α-cell proliferation. In young P1-Pdx1Cre mice (less than 15 weeks) there was a balanced increase in the pancreatic content of insulin and somatostatin, which was associated with normoglycemia. In older P1-Pdx1Cre mice the pancreatic somatostatin content far exceeded that of insulin, leading to the progressive development of severe hypoglycemia beyond 30 weeks. In contrast, in older P1-Ngn3Cre mice the relative increase of the pancreatic insulin content exceeded that of somatostatin and these mice remained normoglycemic. In conclusion, forced expression of PLAG1 under the control of the Pdx1 or Ngn3 promoter in murine pancreas induces different degrees of endocrine hormone imbalances within the pancreas, which is associated with hypoglycemia in P1-Pdx1Cre mice but not P1-Ngn3Cre mice. These results suggest that once stem cell-derived islet transplantations become possible, the appropriate balance between different hormone-producing cells will need to be preserved to prevent deregulated glucose metabolism.

AB - Pleomorphic adenoma gene-like 1 (PLAGL1) has been linked to transient neonatal diabetes mellitus. Here, we investigated the role of the related pleomorphic adenoma gene 1 (PLAG1) in glucose homeostasis. PLAG1 transgenic mice in which expression of the PLAG1 transgene can be targeted to different organs by Cre-mediated modulation were crossed with Pdx1-Cre or Ngn3-Cre mice, resulting in double transgenic P1- Pdx1Cre or P1-Ngn3Cre mice, respectively. P1-Pdx1Cre and P1-Ngn3Cre mice developed hyperplasia of pancreatic islets due to increased β- and δ- but not α-cell proliferation. In young P1-Pdx1Cre mice (less than 15 weeks) there was a balanced increase in the pancreatic content of insulin and somatostatin, which was associated with normoglycemia. In older P1-Pdx1Cre mice the pancreatic somatostatin content far exceeded that of insulin, leading to the progressive development of severe hypoglycemia beyond 30 weeks. In contrast, in older P1-Ngn3Cre mice the relative increase of the pancreatic insulin content exceeded that of somatostatin and these mice remained normoglycemic. In conclusion, forced expression of PLAG1 under the control of the Pdx1 or Ngn3 promoter in murine pancreas induces different degrees of endocrine hormone imbalances within the pancreas, which is associated with hypoglycemia in P1-Pdx1Cre mice but not P1-Ngn3Cre mice. These results suggest that once stem cell-derived islet transplantations become possible, the appropriate balance between different hormone-producing cells will need to be preserved to prevent deregulated glucose metabolism.

UR - http://www.scopus.com/inward/record.url?scp=84930476298&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930476298&partnerID=8YFLogxK

U2 - 10.3727/096368910X550242

DO - 10.3727/096368910X550242

M3 - Article

AN - SCOPUS:84930476298

VL - 20

SP - 1285

EP - 1297

JO - Cell Transplantation

JF - Cell Transplantation

SN - 0963-6897

IS - 8

ER -