Blockade of β1 Integrin–Laminin-5 Interaction Affects Spreading and Insulin Secretion of Rat β-Cells Attached on Extracellular Matrix

Parnaud, Géraldine; Hammar, Eva; Rouiller, D.; Armanet, Mathieu; Halban, Philippe A.; Bosco, Domenico

doi:10.2337/db05-1388

Cited by 118 publications

(116 citation statements)

References 50 publications

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“…Likewise, there are indications that beta cells do not form their own basement membrane, but rely on endothelial cells to form a vascular basement membrane containing LMs next to the beta cell [14]. LM-111 has been demonstrated to promote differentiation of pancreatic precursor cells into beta cells in vitro [24] and to promote glucose-stimulated insulin secretion in vitro [15,25,26]. Prostaglandins exert a number of effects on islet beta cells, although mostly negative [27,28].…”

Section: Discussionmentioning

confidence: 99%

Endothelial cell signalling supports pancreatic beta cell function in the rat

et al. 2009

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Aims/hypothesis The proximity of endothelial cells and beta cells in islets by necessity means that they are exposed to each other's products. Whereas islet endothelial cells require signals from beta cells to function properly, endothelin-1, thrombospondin-1 and laminins, among others, have been identified as endothelial-derived molecules, although their full effects on beta cells have not been explored. We tested the hypothesis that islet endothelialderived products affect beta cell function. Methods Endothelial cells from rat islets were proliferated and purified. Endothelium-conditioned culture medium (ECCM) was obtained by maintaining the endothelial cells in culture medium. Islet function was evaluated following exposure of cultured islets to standard culture medium or ECCM. Changes in mRNA levels for key beta cell metabolic enzymes were also measured in islets after ECCM exposure.Results Glucose-stimulated insulin release and islet insulin content were markedly enhanced by exposure to ECCM. This was at least partly explained by improved mitochondrial function, as assessed by glucose oxidation and an upregulation of the mitochondrial gene for glycerol-3-phosphate dehydrogenase (mGpdh [also known as Gpd2]), combined with upregulation of the rate-limiting enzyme in the glycolysis, glucokinase, in the islets. The intracellular degradation of insulin was also decreased in the islets. Islet endothelial cells produced laminins, and the positive effects of islet endothelial cells were prevented by addition of a neutralising antibody to the β1-chain of laminin. Addition of exogenous laminin stimulated islet function. Conclusions/interpretation This study provides proof of principle that endothelial cells can affect the function of beta cells in their vicinity and that this is at least partially mediated by laminins.

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Section: Discussionmentioning

confidence: 99%

Endothelial cell signalling supports pancreatic beta cell function in the rat

et al. 2009

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“…In rat b-cells, we previously observed that spreading cells secreted more insulin in response to glucose compared with round cells (25). This effect was attributed to outside-in signaling through b1 integrin, which induces phosphorylation of focal adhesion kinase (FAK), a protein that localizes at focal contacts (26,31). Despite distinct molecular structures, some crossroads exist between integrins and cadherins (32).…”

Section: Discussionmentioning

confidence: 99%

Cadherin Engagement Improves Insulin Secretion of Single Human β-Cells

et al. 2014

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The aim of this study was to assess whether cadherinmediated adhesion of human islet cells was affected by insulin secretagogues and explore the role of cadherins in the secretory activity of b-cells. Experiments were carried out with single islet cells adherent to chimeric proteins made of functional E-, N-, or P-cadherin ectodomains fused to the Fc fragment of immunoglobulin (E-cad/Fc, N-cad/Fc, and P-cad/Fc) and immobilized on an inert substrate. We observed that cadherin expression in islet cells was not affected by insulin secretagogues. Adhesion tests showed that islet cells attached to N-cad/Fc and E-cad/Fc acquired, in a timeand secretagogue-dependent manner, a spreading form that was inhibited by blocking cadherin antibodies. By reverse hemolytic plaque assay, we showed that glucosestimulated insulin secretion of single b-cells was increased by N-cad/Fc and E-cad/Fc adhesion compared with control. In the presence of E-cad/Fc and after glucose stimulation, we showed that total insulin secretion was six times higher in spreading b-cells compared with round b-cells. Furthermore, cadherin-mediated adhesion induced an asymmetric distribution of cortical actin in b-cells. Our results demonstrate that adhesion of b-cells to E-and N-cadherins is regulated by insulin secretagogues and that E-and N-cadherin engagement promotes stimulated insulin secretion.

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“…40 Additionally, Hammar et al demonstrated the phosphorylation of FAK upon binding of b-cells to matrix secreted by 804G cells, 41 and more recently, their group has shown that blocking b 1 integrin binding to this matrix inhibited the phosphorylation of FAK. 42 Insulin secretion in response to high glucose concentration (16.7 mM) was measured from MIN6 b-cells cultured in PEG hydrogels presenting matrix interactions. The amount of insulin released per cell was approximately 350% greater in samples containing laminin and 75% greater in those with collagen type IV than that released from b-cells cultured without matrix interactions and cells cultured with the other tested matrix proteins over the 10-day experimental time course (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cell–Matrix Interactions Improve β-Cell Survival and Insulin Secretion in Three-Dimensional Culture

Weber

Hayda

Anseth

2008

Tissue Engineering Part A

209

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Controlled matrix interactions were presented to pancreatic b-cells in three-dimensional culture within poly (ethylene glycol) hydrogels. Dispersed MIN6 b-cells were encapsulated in gel environments containing the following entrapped extracellular matrix (ECM) proteins: collagen type I, collagen type IV, fibrinogen, fibronectin, laminin, and vitronectin. In ECM-containing gels, b-cell survival was significantly better than in gels without ECM over 10 days. Correspondingly, apoptosis in encapsulated b-cells was less in the presence of each matrix protein, suggesting the ability of individual matrix interactions to prevent matrix signaling-related apoptosis (anoikis). MIN6 b-cells cultured in gels containing collagen type IV or laminin secreted more insulin in response to glucose stimulation than b-cells in all other experimental conditions. Variations in collagen type IV or laminin concentration between 10 mg=mL and 250 mg=mL did not affect insulin secretion. Finally, b-cell function in hydrogels presenting both collagen type IV and laminin revealed synergistic interactions. With a total protein concentration of 100 mg=mL, three gel compositions of varying ratios of collagen type IV to laminin (25:75, 50:50, and 75:25) were tested. In the presence of 25 mg=mL of collagen type IV and 75 mg=mL of laminin, bcell insulin secretion was greater than with laminin or collagen type IV individually. These results demonstrate that specific, rationally designed extracellular environments promote isolated b-cell survival and function.

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Blockade of β1 Integrin–Laminin-5 Interaction Affects Spreading and Insulin Secretion of Rat β-Cells Attached on Extracellular Matrix

Cited by 118 publications

References 50 publications

Endothelial cell signalling supports pancreatic beta cell function in the rat

Endothelial cell signalling supports pancreatic beta cell function in the rat

Cadherin Engagement Improves Insulin Secretion of Single Human β-Cells

Cell–Matrix Interactions Improve β-Cell Survival and Insulin Secretion in Three-Dimensional Culture

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