Insulin Secretion and DNA Synthesis of Cultured Islets of Langerhans Are Influenced by the Matrix

Hulinsky, Ilja; Harrington, Joan A.; Cooney, Sue J.; Silink, Martin

doi:10.1097/00006676-199510000-00015

Cited by 21 publications

(12 citation statements)

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“…It is unclear what biological effects Cell-Tak has on cultured cells, and toxicity reports from the literature are conflicting [25,26]. Cell-Tak did not appear to be toxic to the cells used in this study as indicated by the viability analysis.…”

Section: Discussionmentioning

confidence: 79%

Equibiaxial strain stimulates fibroblastic phenotype shift in smooth muscle cells in an engineered tissue model of the aortic wall

2006

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Section: Discussionmentioning

confidence: 79%

Equibiaxial strain stimulates fibroblastic phenotype shift in smooth muscle cells in an engineered tissue model of the aortic wall

2006

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“…Several studies have suggested that ECM and/or BM proteins are required for differentiation of beta cells [32][33][34], survival of islets in culture [15,18] and enhancement of insulin production [35,36]. However, studies of mice have shown that there is no BM in islets of Langerhans, with the exception of vascular BM [11][12][13][14].…”

Section: Discussionmentioning

confidence: 99%

Blood vessels of human islets of Langerhans are surrounded by a double basement membrane

et al. 2008

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Aims/hypothesis Based on mouse study findings, pancreatic islet cells are supposed to lack basement membrane (BM) and interact directly with vascular endothelial BM. Until now, the BM composition of human islets has remained elusive. Methods Immunohistochemistry with specific monoclonal and polyclonal antibodies as well as electron microscopy were used to study BM organisation and composition in human adult islets. Isolated islet cells and function-blocking monoclonal antibodies and recombinant soluble Lutheran peptide were further used to study islet cell adhesion to laminin (Lm)-511. Short-term cultures of islets were used to study Lutheran and integrin distribution. Results Immunohistochemistry revealed a unique organisation for human Lm-511/521 as a peri-islet BM, which coinvaginated into islets with vessels, forming an outer endocrine BM of the intra-islet vascular channels, and was distinct from the vascular BM that additionally contained Lm-411/421. These findings were verified by electron microscopy. Lutheran glycoprotein, a receptor for the Lm α5 chain, was found prominently on endocrine cells, as identified by immunohistochemistry and RT-PCR,

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“…Islets of Langerhans lose glucose responsiveness when maintained for several days in culture. It has been shown that a better preservation of an insulin response to glucose was largely dependent on the substrate used for maintaining the cells in culture (5,27,29). These studies primarily addressed the longterm (days) preservation and growth of primary islet cells in culture.…”

Section: Discussionmentioning

confidence: 99%

Importance of cell-matrix interactions in rat islet beta-cell secretion in vitro: role of alpha6beta1 integrin.

et al. 2000

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It has long been recognized that islet cell function is rapidly altered in vitro, but can be maintained, at least in part, when cells are layered on defined extracellular matrices. The present work addresses the influence of short-term cell-matrix interactions on islet -cell function and provides first insight into the molecular basis of these interactions. When primary rat -cells were allowed to attach to a matrix produced by a rat carcinoma cell line (804G), there was an increased insulin secretory response to secretagogues. This change was the result of an increase in the proportion of actively secreting -cells and in the amount of insulin secreted per active cell, as shown using the reverse hemolytic plaque assay. In turn, the spreading or flattening of -cells on this matrix was enhanced by secretagogues, and flattened cells secreted more insulin than rounded cells. Using indirect immunofluorescence, it was found that 1) 6 1 integrins are present at the surface of islet cells in situ, 2) 6 1 expression is heterogeneous among purified -cells and is upregulated by insulin secretagogues, 3) 6 1 expression is higher in spreading cells, and 4) anti-6 1 -s p e c i fic antibodies decrease spreading. These observations demonstrate that islet cell-matrix interactions can improve the sensitivity of insulin cells to glucose and are mediated, at least in part, by 6 1 integrins, suggesting that outside-in signaling through 6 1 integrin plays a major role in the regulation of -cell function. Diabetes 49:233-243, 2000 P rimary cells of rat islets of Langerhans lose glucose responsiveness and eventually die when maintained in culture for a long period of time. By contrast, the secretory capability of islet cells remains stable when dishes are first coated with components of extracellular matrices (ECMs) (1). Thus, adult rat islets maintained over several weeks on ECM respond to an acute glucose stimulation by a five-to eightfold increase in insulin secretion (2). In human -cells cultured 5-11 days on bovine corneal endothelial cell matrix, both basal and stimulated insulin release were also increased, compared with cells layered on gelatin, collagen, or Matrigel (3). Furthermore, when overlaid with collagen, monolayers of human islet cells undergo a gradual and complete reorganization into a threedimensional islet-like structure with a striking reinforcement of their secretory activity. Under these conditions, cells were able to survive more than 8 weeks (4). By contrast, standard cultures on uncoated plastic petri dishes exhibit a rapid and d e finitive decline in insulin secretion with a survival time not exceeding 14 days (4). Using a reverse hemolytic plaque a s s a y, Perfetti et al. (5) determined that -cells cultured for 6 weeks on Matrigel showed an equal number of insulinsecreting cells compared with freshly isolated islets cultured for only 3 days in the absence of Matrigel. The amount of insulin released per single -cell was nevertheless reduced by as much as 60%. Despite this evidence for a crucial role of islet...

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Insulin Secretion and DNA Synthesis of Cultured Islets of Langerhans Are Influenced by the Matrix

Cited by 21 publications

References 0 publications

Equibiaxial strain stimulates fibroblastic phenotype shift in smooth muscle cells in an engineered tissue model of the aortic wall

Equibiaxial strain stimulates fibroblastic phenotype shift in smooth muscle cells in an engineered tissue model of the aortic wall

Blood vessels of human islets of Langerhans are surrounded by a double basement membrane

Importance of cell-matrix interactions in rat islet beta-cell secretion in vitro: role of alpha6beta1 integrin.

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