Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated β-cell maturation

Louise Winkel, Annika Bagge, Louise Larsen, Tobias N. Haase, Morten Rasmussen, Jeanette Lykke, Dennis B. Holmgaard, Lars Thim, Jens Høiriis Nielsen, Louise Torp Dalgaard

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

The endocrine pancreas expands markedly in the first postnatal days and the insulin producing β-cells initiate a functional maturation preceded by a morphological change of the islets of Langerhans. Trefoil factor 3 (TFF3) is a secreted peptide expressed in intestinal epithelia, where it promotes migration, but its role in the pancreas is not characterized. The aim of this study was to examine the expression and function of TFF3 in perinatal rat pancreas, ex vivo cultured fetal rat pancreas and in the rat β-cell line INS-1E. Control or gestational low-protein diet perinatal rat pancreas was harvested at embryonic day 20 (E20), day of birth (P0) and postnatal day 2 (P2). TFF3 mRNA was upregulated 4.5-fold at P0 vs. E20 and downregulated again at P2. In protein-undernourished pups induction of TFF3 at P0 was further increased to 9.7-fold and was increased at P2. TFF3 caused tyrosine phosphorylation of EGFR in INS-1E β-cells, and purified recombinant TFF3 increased both attachment and spreading of INS-1E β-cells. In ex vivo cultures of collagenase digested fetal rat pancreas, a model of perinatal β-cell maturation, TFF3 increased cellular spreading as well as insulin mRNA levels. TFF3 also increased the expression of Pref1/Dlk1 that shares similarities in expression and regulation with TFF3. These results suggest that TFF3 may promote adhesion and spreading of cells to accelerate β-cell maturation. This study indicates a functional role for TFF3 in pancreatic β-cell maturation in the perinatal period, which is altered by low protein diet during gestation.
OriginalsprogEngelsk
Artikelnummere1472186
TidsskriftIslets
Vol/bind10
Udgave nummer3
ISSN1938-2014
DOI
StatusUdgivet - 2018

Bibliografisk note

“This is an Accepted Manuscript of an article published by Taylor & Francis in Islets on 03 May 2018, available online: http://www.tandfonline.com/10.1080/19382014.2018.1472186.”

Citer dette

Winkel, Louise ; Bagge, Annika ; Larsen, Louise ; Haase, Tobias N. ; Rasmussen, Morten ; Lykke, Jeanette ; Holmgaard, Dennis B. ; Thim, Lars ; Nielsen, Jens Høiriis ; Dalgaard, Louise Torp. / Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated β-cell maturation. I: Islets. 2018 ; Bind 10, Nr. 3.
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title = "Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated β-cell maturation",
abstract = "The endocrine pancreas expands markedly in the first postnatal days and the insulin producing β-cells initiate a functional maturation preceded by a morphological change of the islets of Langerhans. Trefoil factor 3 (TFF3) is a secreted peptide expressed in intestinal epithelia, where it promotes migration, but its role in the pancreas is not characterized. The aim of this study was to examine the expression and function of TFF3 in perinatal rat pancreas, ex vivo cultured fetal rat pancreas and in the rat β-cell line INS-1E. Control or gestational low-protein diet perinatal rat pancreas was harvested at embryonic day 20 (E20), day of birth (P0) and postnatal day 2 (P2). TFF3 mRNA was upregulated 4.5-fold at P0 vs. E20 and downregulated again at P2. In protein-undernourished pups induction of TFF3 at P0 was further increased to 9.7-fold and was increased at P2. TFF3 caused tyrosine phosphorylation of EGFR in INS-1E β-cells, and purified recombinant TFF3 increased both attachment and spreading of INS-1E β-cells. In ex vivo cultures of collagenase digested fetal rat pancreas, a model of perinatal β-cell maturation, TFF3 increased cellular spreading as well as insulin mRNA levels. TFF3 also increased the expression of Pref1/Dlk1 that shares similarities in expression and regulation with TFF3. These results suggest that TFF3 may promote adhesion and spreading of cells to accelerate β-cell maturation. This study indicates a functional role for TFF3 in pancreatic β-cell maturation in the perinatal period, which is altered by low protein diet during gestation.",
author = "Louise Winkel and Annika Bagge and Louise Larsen and Haase, {Tobias N.} and Morten Rasmussen and Jeanette Lykke and Holmgaard, {Dennis B.} and Lars Thim and Nielsen, {Jens H{\o}iriis} and Dalgaard, {Louise Torp}",
note = "“This is an Accepted Manuscript of an article published by Taylor & Francis in Islets on 03 May 2018, available online: http://www.tandfonline.com/10.1080/19382014.2018.1472186.”",
year = "2018",
doi = "10.1080/19382014.2018.1472186",
language = "English",
volume = "10",
journal = "Islets",
issn = "1938-2014",
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Winkel, L, Bagge, A, Larsen, L, Haase, TN, Rasmussen, M, Lykke, J, Holmgaard, DB, Thim, L, Nielsen, JH & Dalgaard, LT 2018, 'Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated β-cell maturation' Islets, bind 10, nr. 3, e1472186. https://doi.org/10.1080/19382014.2018.1472186

Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated β-cell maturation. / Winkel, Louise ; Bagge, Annika; Larsen, Louise; Haase, Tobias N.; Rasmussen, Morten; Lykke, Jeanette; Holmgaard, Dennis B.; Thim, Lars; Nielsen, Jens Høiriis; Dalgaard, Louise Torp.

I: Islets, Bind 10, Nr. 3, e1472186, 2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated β-cell maturation

AU - Winkel, Louise

AU - Bagge, Annika

AU - Larsen, Louise

AU - Haase, Tobias N.

AU - Rasmussen, Morten

AU - Lykke, Jeanette

AU - Holmgaard, Dennis B.

AU - Thim, Lars

AU - Nielsen, Jens Høiriis

AU - Dalgaard, Louise Torp

N1 - “This is an Accepted Manuscript of an article published by Taylor & Francis in Islets on 03 May 2018, available online: http://www.tandfonline.com/10.1080/19382014.2018.1472186.”

PY - 2018

Y1 - 2018

N2 - The endocrine pancreas expands markedly in the first postnatal days and the insulin producing β-cells initiate a functional maturation preceded by a morphological change of the islets of Langerhans. Trefoil factor 3 (TFF3) is a secreted peptide expressed in intestinal epithelia, where it promotes migration, but its role in the pancreas is not characterized. The aim of this study was to examine the expression and function of TFF3 in perinatal rat pancreas, ex vivo cultured fetal rat pancreas and in the rat β-cell line INS-1E. Control or gestational low-protein diet perinatal rat pancreas was harvested at embryonic day 20 (E20), day of birth (P0) and postnatal day 2 (P2). TFF3 mRNA was upregulated 4.5-fold at P0 vs. E20 and downregulated again at P2. In protein-undernourished pups induction of TFF3 at P0 was further increased to 9.7-fold and was increased at P2. TFF3 caused tyrosine phosphorylation of EGFR in INS-1E β-cells, and purified recombinant TFF3 increased both attachment and spreading of INS-1E β-cells. In ex vivo cultures of collagenase digested fetal rat pancreas, a model of perinatal β-cell maturation, TFF3 increased cellular spreading as well as insulin mRNA levels. TFF3 also increased the expression of Pref1/Dlk1 that shares similarities in expression and regulation with TFF3. These results suggest that TFF3 may promote adhesion and spreading of cells to accelerate β-cell maturation. This study indicates a functional role for TFF3 in pancreatic β-cell maturation in the perinatal period, which is altered by low protein diet during gestation.

AB - The endocrine pancreas expands markedly in the first postnatal days and the insulin producing β-cells initiate a functional maturation preceded by a morphological change of the islets of Langerhans. Trefoil factor 3 (TFF3) is a secreted peptide expressed in intestinal epithelia, where it promotes migration, but its role in the pancreas is not characterized. The aim of this study was to examine the expression and function of TFF3 in perinatal rat pancreas, ex vivo cultured fetal rat pancreas and in the rat β-cell line INS-1E. Control or gestational low-protein diet perinatal rat pancreas was harvested at embryonic day 20 (E20), day of birth (P0) and postnatal day 2 (P2). TFF3 mRNA was upregulated 4.5-fold at P0 vs. E20 and downregulated again at P2. In protein-undernourished pups induction of TFF3 at P0 was further increased to 9.7-fold and was increased at P2. TFF3 caused tyrosine phosphorylation of EGFR in INS-1E β-cells, and purified recombinant TFF3 increased both attachment and spreading of INS-1E β-cells. In ex vivo cultures of collagenase digested fetal rat pancreas, a model of perinatal β-cell maturation, TFF3 increased cellular spreading as well as insulin mRNA levels. TFF3 also increased the expression of Pref1/Dlk1 that shares similarities in expression and regulation with TFF3. These results suggest that TFF3 may promote adhesion and spreading of cells to accelerate β-cell maturation. This study indicates a functional role for TFF3 in pancreatic β-cell maturation in the perinatal period, which is altered by low protein diet during gestation.

U2 - 10.1080/19382014.2018.1472186

DO - 10.1080/19382014.2018.1472186

M3 - Journal article

VL - 10

JO - Islets

JF - Islets

SN - 1938-2014

IS - 3

M1 - e1472186

ER -