Inhibition of Beta Cell Growth and Function by Bone Morphogenetic Proteins

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2014 Sep 28

PMID 25260823

Citations 18

Authors

Christine Bruun

Gitte L Christensen

Marie L B Jacobsen

Marianne B Kanstrup

Pernille R Jensen

Helle Fjordvang

Thomas Mandrup-Poulsen

Nils Billestrup

Affiliations

Soon will be listed here.

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.

Citing Articles

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HAMSAB diet ameliorates dysfunctional signaling in pancreatic islets in autoimmune diabetes.

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A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.

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Beta cell dysfunction induced by bone morphogenetic protein (BMP)-2 is associated with histone modifications and decreased NeuroD1 chromatin binding.

Urizar A, Prause M, Ingerslev L, Wortham M, Sui Y, Sander M Cell Death Dis. 2023; 14(7):399.

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High glucose promotes the progression of colorectal cancer by activating the BMP4 signaling and inhibited by glucagon-like peptide-1 receptor agonist.

Ma B, Wang X, Ren H, Li Y, Zhang H, Yang M BMC Cancer. 2023; 23(1):594.

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