Inhibition of beta cell growth and function by bone morphogenetic proteins

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Inhibition of beta cell growth and function by bone morphogenetic proteins. / Bruun, Christine; Christensen, Gitte Lund; Jacobsen, Marie L B; Kanstrup, Marianne B; Jensen, Pernille R; Fjordvang, Helle; Mandrup-Poulsen, Thomas; Billestrup, Nils.

I: Diabetologia, Bind 57, Nr. 12, 27.09.2014, s. 2546-54.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Bruun, C, Christensen, GL, Jacobsen, MLB, Kanstrup, MB, Jensen, PR, Fjordvang, H, Mandrup-Poulsen, T & Billestrup, N 2014, 'Inhibition of beta cell growth and function by bone morphogenetic proteins', Diabetologia, bind 57, nr. 12, s. 2546-54. https://doi.org/10.1007/s00125-014-3384-8

APA

Bruun, C., Christensen, G. L., Jacobsen, M. L. B., Kanstrup, M. B., Jensen, P. R., Fjordvang, H., Mandrup-Poulsen, T., & Billestrup, N. (2014). Inhibition of beta cell growth and function by bone morphogenetic proteins. Diabetologia, 57(12), 2546-54. https://doi.org/10.1007/s00125-014-3384-8

Vancouver

Bruun C, Christensen GL, Jacobsen MLB, Kanstrup MB, Jensen PR, Fjordvang H o.a. Inhibition of beta cell growth and function by bone morphogenetic proteins. Diabetologia. 2014 sep 27;57(12):2546-54. https://doi.org/10.1007/s00125-014-3384-8

Author

Bruun, Christine ; Christensen, Gitte Lund ; Jacobsen, Marie L B ; Kanstrup, Marianne B ; Jensen, Pernille R ; Fjordvang, Helle ; Mandrup-Poulsen, Thomas ; Billestrup, Nils. / Inhibition of beta cell growth and function by bone morphogenetic proteins. I: Diabetologia. 2014 ; Bind 57, Nr. 12. s. 2546-54.

Bibtex

@article{bfc588dc880d4bdda20d8d473131913b,
title = "Inhibition of beta cell growth and function by bone morphogenetic proteins",
abstract = "AIMS/HYPOTHESIS: Impairment of beta cell mass and function is evident in both type 1 and type 2 diabetes. In healthy physiological conditions pancreatic beta cells adapt to the body's increasing insulin requirements by proliferation and improved function. We hypothesised that during the development of diabetes, there is an increase in the expression of inhibitory factors that prevent the beta cells from adapting to the increased need for insulin. We evaluated the effects of bone morphogenetic protein (BMP) 2 and -4 on beta cells.METHODS: The effects of BMP2 and -4 on beta cell proliferation, apoptosis, gene expression and insulin release were studied in isolated islets of Langerhans from rats, mice and humans. The expression of BMPs was analysed by immunocytochemistry and real-time PCR. The role of endogenous BMP was investigated using a soluble and neutralising form of the BMP receptor 1A.RESULTS: BMP2 and -4 were found to inhibit basal as well as growth factor-stimulated proliferation of primary beta cells from rats and mice. Bmp2 and Bmp4 mRNA and protein were expressed in islets and regulated by inflammatory cytokines. Neutralisation of endogenous BMP activity resulted in enhanced proliferation of rodent beta cells. The expression of Id mRNAs was induced by BMP4 in rat and human islets. Finally, glucose-induced insulin secretion was significantly impaired in rodent and human islets pre-treated with BMP4, and inhibition of BMP activity resulted in enhanced insulin release.CONCLUSIONS/INTERPRETATION: These data show that BMP2 and -4 exert inhibitory actions on beta cells in vitro and suggest that BMPs exert regulatory roles of beta cell growth and function.",
author = "Christine Bruun and Christensen, {Gitte Lund} and Jacobsen, {Marie L B} and Kanstrup, {Marianne B} and Jensen, {Pernille R} and Helle Fjordvang and Thomas Mandrup-Poulsen and Nils Billestrup",
year = "2014",
month = sep,
day = "27",
doi = "10.1007/s00125-014-3384-8",
language = "English",
volume = "57",
pages = "2546--54",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "12",

}

RIS

TY - JOUR

T1 - Inhibition of beta cell growth and function by bone morphogenetic proteins

AU - Bruun, Christine

AU - Christensen, Gitte Lund

AU - Jacobsen, Marie L B

AU - Kanstrup, Marianne B

AU - Jensen, Pernille R

AU - Fjordvang, Helle

AU - Mandrup-Poulsen, Thomas

AU - Billestrup, Nils

PY - 2014/9/27

Y1 - 2014/9/27

N2 - AIMS/HYPOTHESIS: Impairment of beta cell mass and function is evident in both type 1 and type 2 diabetes. In healthy physiological conditions pancreatic beta cells adapt to the body's increasing insulin requirements by proliferation and improved function. We hypothesised that during the development of diabetes, there is an increase in the expression of inhibitory factors that prevent the beta cells from adapting to the increased need for insulin. We evaluated the effects of bone morphogenetic protein (BMP) 2 and -4 on beta cells.METHODS: The effects of BMP2 and -4 on beta cell proliferation, apoptosis, gene expression and insulin release were studied in isolated islets of Langerhans from rats, mice and humans. The expression of BMPs was analysed by immunocytochemistry and real-time PCR. The role of endogenous BMP was investigated using a soluble and neutralising form of the BMP receptor 1A.RESULTS: BMP2 and -4 were found to inhibit basal as well as growth factor-stimulated proliferation of primary beta cells from rats and mice. Bmp2 and Bmp4 mRNA and protein were expressed in islets and regulated by inflammatory cytokines. Neutralisation of endogenous BMP activity resulted in enhanced proliferation of rodent beta cells. The expression of Id mRNAs was induced by BMP4 in rat and human islets. Finally, glucose-induced insulin secretion was significantly impaired in rodent and human islets pre-treated with BMP4, and inhibition of BMP activity resulted in enhanced insulin release.CONCLUSIONS/INTERPRETATION: These data show that BMP2 and -4 exert inhibitory actions on beta cells in vitro and suggest that BMPs exert regulatory roles of beta cell growth and function.

AB - AIMS/HYPOTHESIS: Impairment of beta cell mass and function is evident in both type 1 and type 2 diabetes. In healthy physiological conditions pancreatic beta cells adapt to the body's increasing insulin requirements by proliferation and improved function. We hypothesised that during the development of diabetes, there is an increase in the expression of inhibitory factors that prevent the beta cells from adapting to the increased need for insulin. We evaluated the effects of bone morphogenetic protein (BMP) 2 and -4 on beta cells.METHODS: The effects of BMP2 and -4 on beta cell proliferation, apoptosis, gene expression and insulin release were studied in isolated islets of Langerhans from rats, mice and humans. The expression of BMPs was analysed by immunocytochemistry and real-time PCR. The role of endogenous BMP was investigated using a soluble and neutralising form of the BMP receptor 1A.RESULTS: BMP2 and -4 were found to inhibit basal as well as growth factor-stimulated proliferation of primary beta cells from rats and mice. Bmp2 and Bmp4 mRNA and protein were expressed in islets and regulated by inflammatory cytokines. Neutralisation of endogenous BMP activity resulted in enhanced proliferation of rodent beta cells. The expression of Id mRNAs was induced by BMP4 in rat and human islets. Finally, glucose-induced insulin secretion was significantly impaired in rodent and human islets pre-treated with BMP4, and inhibition of BMP activity resulted in enhanced insulin release.CONCLUSIONS/INTERPRETATION: These data show that BMP2 and -4 exert inhibitory actions on beta cells in vitro and suggest that BMPs exert regulatory roles of beta cell growth and function.

U2 - 10.1007/s00125-014-3384-8

DO - 10.1007/s00125-014-3384-8

M3 - Journal article

C2 - 25260823

VL - 57

SP - 2546

EP - 2554

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 12

ER -

ID: 124429590