Regulation of beta-cell mass by hormones and growth factors.

Nielsen, Jens Høiriis; Galsgaard, Elisabeth D.; Møldrup, Annette; Friedrichsen, Birgitte Nissen; Billestrup, Nils; Hansen, Jens Aage; Lee, Ying C.; Carlsson, Carina

doi:10.2337/diabetes.50.2007.s25

Cited by 216 publications

(159 citation statements)

References 38 publications

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“…Although there is abundant evidence that these agents increase in vivo islet growth and β-cell mass, as well as in vitro replication of rodent β-cells and insulinoma cell lines, 26,[43][44][45] we are unaware of similar data that unequivocally demonstrates a stimulatory effect on human β-cells in vitro. In support of our finding, the in vitro proliferative responses of highly purified rat and human β-cells have been compared.…”

Section: Discussionmentioning

confidence: 99%

“…To test this hypothesis Id3 treated β-cells were exposed to agents which have been reported to induce β-cell replication: prolactin and exendin-4 [an analoe of glucagon-like peptide-1 (GLP-1)]. 26,[43][44][45] Treatment of Id3-expressing β-cells with either prolactin or exendin-4 had a synergistic effect on BrdU incorporation, with the percentage of BrdU + β-cells increasing from 34.7 ± 2.9%, to 56.7 ± 3.3% in the presence of prolactin, and to 78.7 ± 5.8% in the presence of exendin-4 (Fig. 1E, F and H).…”

Section: E and F)mentioning

confidence: 99%

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Id3 upregulates BrdU incorporation associated with a DNA damage response, not replication, in human pancreatic β-cells

Lee

Hao

Levine

et al. 2011

Islets

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Section: Discussionmentioning

confidence: 99%

Section: E and F)mentioning

confidence: 99%

Id3 upregulates BrdU incorporation associated with a DNA damage response, not replication, in human pancreatic β-cells

Lee

Hao

Levine

et al. 2011

Islets

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“…Development of efficient ways for in vitro expansion of normal islets would significantly advance the prospects of diabetes cell therapy. Adult islet cells are difficult to propagate in culture, although they maintain a proliferative capacity, as evidenced by a limited mitogenic response to a number of growth factors [1,2]. Members of the growth hormone family, in particular placental lactogen (PL) and prolactin (PRL), induce replication in neonatal rat islet cells [3].…”

Section: Introductionmentioning

confidence: 99%

Growth Factor‐Dependent Proliferation of the Pancreatic β‐cell Line βTC‐tet: An Assay for β‐cell Mitogenic Factors

Milo-Landesman

Efrat

2001

Journal of Diabetes Research

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The ability to expand normal pancreatic islet β cells in culture would significantly advance the prospects of cell therapy for diabetes. A number of growth factors can stimulate limited islet cell replication, however other factors may exist which are more effective β-cell-specific mitogens. The search for novel β-cell growth factors has been hampered by the lack of a β-cell-specific proliferation assay. We developed a simple and sensitive assay for β-cell growth factors based on a conditionally-transformed mouse β-cell line (βTC-tet). These cells express the SV40 T antigen (Tag) oncoprotein under control of the tetracycline (Tc) operon regulatory system. In the presence of Tc, Tag expression is tightly shut off and the cells undergo complete growth arrest. Here we show that the growth-arrested cells can proliferate in response to growth factors in the absence of Tag. Using this assay, a number of growth factors previously shown to be mitogenic to a mixed islet cell population were found to induce proliferation of pure β cells. We conclude that growth-arrested βTC-tet cells can be employed in a survey of factors from various sources for identifying novel factors with β-cell mitogenic activity.Key words: β-cell lines, cell proliferation, growth factors, mitogenicity, tetracycline-regulated gene expression INTRODUCTIONBeta-cell transplantation represents an attractive approach for replacement of the ____________________ *Corresponding author: tel: 972-3-640 7701; fax. 972-3-640 9950; e-mail: sefrat@post.tau.ac.il Int. Jnl. Experimental Diab. Res., 3:69-74, 2002 © 2002 Taylor and Francis 1560 damaged β cells in type I diabetes. One major obstacle to β-cell therapy is the lack of an abundant cell supply. A number of rodent β-cell lines have been developed by oncogenic transformation, however this approach has proven difficult to adapt to human β cells. Development of efficient ways for in vitro expansion of normal islets would significantly advance the prospects of diabetes cell therapy. Adult islet cells are difficult to propagate in culture, although they maintain a proliferative capacity, as evidenced by a limited mitogenic response to a number of growth factors [1,2]. Members of the growth hormone family, in particular placental lactogen (PL) and prolactin (PRL), induce replication in neonatal rat islet cells [3]. These activities may be responsible for islet mass expansion in pregnancy. Significant mitogenic effects of hepatocyte growth factor (HGF) have been observed on human fetal and adult islets [4] and mouse islets [5]. Insulin-like growth factors (IGF) I and II, and platelet-derived growth factor, affect fetal rat islet cell growth [6,7]. IGF I has also been shown to stimulate replication of cultured rat insulinoma cells [8], and IGF II activates the growth of both normal [9] and transformed [10] mouse β cells in vivo. The Reg protein, produced by pancreatic acinar cells and regenerating islets, is another candidate for a β-cell growth factor [11]. These findings suggest that islet cells possess cell su...

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“…During this time, limited β-cell replication can be stimulated by various agents; growth factors, vitamin supplements and metabolites leading to a small number of population doublings of rodent insulin-positive cells. 63 Attempts at culturing adult human islet cells resulted in a similar loss of β-cell markers in the proliferating cells following a small number of cell-population doublings. 64,65 Cultured human islets have been shown to expand in vitro as epithelial cells expressing Pdx-1, 66 and have been shown to undergo epithelial-mesenchymal transition to give fibroblastoid cells which expand and redifferentiate into aggregates of epithelial cells with low level expression of islet endocrine genes.…”

confidence: 99%