The ghrelin gene products and exendin-4 promote survival of human pancreatic islet endothelial cells in hyperglycaemic conditions, through phosphoinositide 3-kinase/Akt, extracellular signal-related kinase (ERK)1/2 and cAMP/protein kinase A (PKA) signalling pathways

Favaro, Enrica; Granata, Riccarda; Miceli, Ilaria; Baragli, Alessandra; Settanni, Fabio; Perin, Paolo Cavallo; Ghigo, Ezio; Camussi, Giovanni; Zanone, Maria M.

doi:10.1007/s00125-011-2423-y

Cited by 86 publications

(80 citation statements)

References 49 publications

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“…Macro-and microvascular endothelial cells (ECs) are certainly CD105-positive, but this accessory receptor is also highly expressed by a range of other cell types including bone marrow-and tissue-derived mesenchymal stromal cell (MSC)-like populations. In accordance with this, we have recently isolated from human islets, and expanded in vitro, a population of CD105-expressing cells that are clearly not MECs, but which share phenotypic characteristics with other cells that have been immuno-isolated on the basis of CD105 expression and identified as islet MECs for in vitro studies [1][2][3][4][5].…”

Section: Ecmentioning

confidence: 64%

“…Endothelial cell MEC Microvascular endothelial cell MSC Mesenchymal stromal cell TGF-β Transforming growth factor-β To the Editor: We read with interest the recent report by Favaro et al [1] suggesting that microvascular endothelial cells (MECs) isolated from human islets of Langerhans could be protected from hyperglycaemia-induced apoptosis by gastrointestinal peptides. In this study, as in several previous studies [2][3][4][5], the MECs were expanded in vitro from a population that had been isolated from dispersed human islet cells using anti-CD105 immunobeads.…”

Section: Ecmentioning

confidence: 99%

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Endoglin (CD105) is not a specific selection marker for endothelial cells in human islets of Langerhans

et al. 2012

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Abbreviations ECEndothelial cell MEC Microvascular endothelial cell MSC Mesenchymal stromal cell TGF-β Transforming growth factor-β To the Editor: We read with interest the recent report by Favaro et al [1] suggesting that microvascular endothelial cells (MECs) isolated from human islets of Langerhans could be protected from hyperglycaemia-induced apoptosis by gastrointestinal peptides. In this study, as in several previous studies [2][3][4][5], the MECs were expanded in vitro from a population that had been isolated from dispersed human islet cells using anti-CD105 immunobeads. CD105 (also known as endoglin) is a membrane glycoprotein that acts with transforming growth factor (TGF)-β receptors as an auxiliary binding protein for members of the TGF-β family, including activin, TGF-β1/β3 and bone morphogenic proteins. Macro-and microvascular endothelial cells (ECs) are certainly CD105-positive, but this accessory receptor is also highly expressed by a range of other cell types including bone marrow-and tissue-derived mesenchymal stromal cell (MSC)-like populations. In accordance with this, we have recently isolated from human islets, and expanded in vitro, a population of CD105-expressing cells that are clearly not MECs, but which share phenotypic characteristics with other cells that have been immuno-isolated on the basis of CD105 expression and identified as islet MECs for in vitro studies [1][2][3][4][5].Our cell population was isolated and expanded essentially as described for MSCs [6]. Briefly, human islets (obtained from the King's College London Human Islet Isolation Unit, with appropriate ethics approval) were dissociated by incubation in 0.02% (wt/vol.) EDTA solution with trituration. Cells were resuspended in Dulbecco's Modified Eagle's Medium supplemented with L-glutamine (2 mM), penicillin (100 U/ml), streptomycin (172 μmol/l) and FCS (10% vol./ vol.), seeded in six-well tissue culture dishes and incubated at 37°C in a humidified atmosphere containing 5%/95% CO 2 /air. The medium was changed after 24 h, with removal of non-adherent cells, and when adherent cultures reached confluence, they were trypsinised and subcultured into tissue culture flasks. These cells are likely to be a heterogeneous population of adherent islet stromal cells, including fibroblasts, myofibroblasts and pericytes, as well as MSCs with differentiation potential. In accordance with this, the cells possessed many of the attributes associated with MSCs [6,7], rather than MECs, as shown in Fig. 1. They did not exhibit the typical cobble-stone morphology of monolayer ECs (Fig. 1a-c (Fig. 1d). Cells within this population were multipotent and differentiated in vitro along adipogenic (Fig. 1f), osteogenic (Fig. 1g) and chondrogenic ( Fig. 1h) lineages, assessed by positive oil red O, alizarin red and alcian blue staining, respectively. Flow cytometry demonstrated that they expressed cell surface antigens typically associated with MSCs, including CD105, CD13, CD44, CD73 and CD90, but did not express cell surface antigens characteristic...

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Section: Ecmentioning

confidence: 64%

Section: Ecmentioning

confidence: 99%

Endoglin (CD105) is not a specific selection marker for endothelial cells in human islets of Langerhans

et al. 2012

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“…The ghrelin genederived peptides and exendin-4 exert cyto-protective effects in human pancreatic islet endothelial cells. These antiapoptotic effects involve the phosphoinositide 3-kinase [PI3K]/Akt, extracellular signal-regulated kinase1/2 (ERK1/2) and cAMP/PKA pathways [109]. Although ageing is characterised by a low level of beta cell proliferation, mice treated with exendin-4 at different ages show low glucose levels, suggesting a potential beneficial effect in ageing [110].…”

Section: Contributors To Maintenance Of Islet Cell Mass In Adult Rodentsmentioning

confidence: 99%

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Mezza

Kulkarni

2014

Diabetologia

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Regeneration of mature cells that produce functional insulin represents a major focus and a challenge of current diabetes research aimed at restoring beta cell mass in patients with most forms of diabetes, as well as in ageing. The capacity to adapt to diverse physiological states during life and the consequent ability to cope with increased metabolic demands in the normal regulation of glucose homeostasis is a distinctive feature of the endocrine pancreas in mammals. Both beta and alpha cells, and presumably other islet cells, are dynamically regulated via nutrient, neural and/or hormonal activation of growth factor signalling and the post-transcriptional modification of a variety of genes or via the microbiome to continually maintain a balance between regeneration (e.g. proliferation, neogenesis) and apoptosis. Here we review key regulators that determine islet cell mass at different ages in mammals. Understanding the chronobiology and the dynamics and agedependent processes that regulate the relationship between the different cell types in the overall maintenance of an optimally functional islet cell mass could provide important insights into planning therapeutic approaches to counter and/or prevent the development of diabetes.

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“…Among the wide range of common biological functions, acylated and unacylated ghrelin exert a protective activity on several cell lines including cardiac and endothelial cells, pancreatic b cells, islets, and islet microendothelial cells, cortical neurons, vascular smooth muscle cells, and visceral adipocytes (Baldanzi et al 2002;Chung et al 2008;Favaro et al 2012;Granata et al 2007;Hwang et al 2009;Rodríguez et al 2012;Zhan et al 2008). Both peptides promote the differentiation of skeletal myoblasts, preadipocytes, and embryonic stem cells toward cardiomyocytes (Filigheddu et al 2007;Gao et al 2012Gao et al , 2013Giovambattista et al 2008;Miegueu et al 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Both peptides promote the differentiation of skeletal myoblasts, preadipocytes, and embryonic stem cells toward cardiomyocytes (Filigheddu et al 2007;Gao et al 2012Gao et al , 2013Giovambattista et al 2008;Miegueu et al 2011). Moreover, they affect, either positively or negatively, proliferation of numerous cell types including osteoblasts, pancreatic b cells, islets and islet microendothelial cells, myoblasts, and adrenocortical tumor cells (Delhanty et al 2006(Delhanty et al , 2007Favaro et al 2012;Filigheddu et al 2007;Granata et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Ghrelin Gene Products in Acute and Chronic Inflammation

Prodam,

Filigheddu

2014

Arch. Immunol. Ther. Exp.

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Ghrelin gene products-the peptides ghrelin, unacylated ghrelin, and obestatin-have several actions on the immune system, opening new perspectives within neuroendocrinology, metabolism and inflammation. The aim of this review is to summarize the available evidence regarding the less known role of these peptides in the machinery of inflammation and autoimmunity, outlining some of their most promising therapeutic applications.

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The ghrelin gene products and exendin-4 promote survival of human pancreatic islet endothelial cells in hyperglycaemic conditions, through phosphoinositide 3-kinase/Akt, extracellular signal-related kinase (ERK)1/2 and cAMP/protein kinase A (PKA) signalling pathways

Cited by 86 publications

References 49 publications

Endoglin (CD105) is not a specific selection marker for endothelial cells in human islets of Langerhans

Endoglin (CD105) is not a specific selection marker for endothelial cells in human islets of Langerhans

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Ghrelin Gene Products in Acute and Chronic Inflammation

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