MIN6 β-cell–β-cell interactions influence insulin secretory responses to nutrients and non-nutrients

Luther, Melanie J.; Hauge-Evans, Astrid C.; Souza, Kleber L.A.; Jörns, Anne; Lenzen, Sigurd; Persaud, Shanta J.; Jones, Peter M.

doi:10.1016/j.bbrc.2006.02.003

Cited by 87 publications

(93 citation statements)

References 41 publications

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“…Toward Cell Clusters Consistent with previous observations, [5][6][7]12,24,37 PANC-1 cells at and near confluence formed 3D multicellular clusters when cultured in SFM (Supplementary Movie S1). In an attempt to explain the sixfold increase in migration rate and subsequent clustering of pancreatic cells upon the removal of serum, Hardikar et al suggested that serum could contain ''inhibitory factors'' that restrict cell migration.…”

Section: Panc-1 Cells Do Not Exhibit Preferential Migrationsupporting

confidence: 90%

“…2,5,12,27,30 The upregulation of islet cell hormone genes (e.g., insulin, glucagon, c-peptide, and somatostatin) and their secretion are associated with clustering and the transition from a two-dimensional monolayer to three-dimensional islet-like structures in vitro. [5][6][7]24,37 Further supporting the importance of the 3D structure is the observation that the secretory responsiveness of cells in 3D clusters was lost upon dispersal of the cells and established again after 3D isletlike structures were reformed. attractive candidates.…”

Section: Introductionmentioning

confidence: 92%

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Pancreatic Epithelial Cells Form Islet-Like Clusters in the Absence of Directed Migration

et al. 2015

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Abstract-The endocrine differentiation of pancreatic ductal epithelial cells is dependent upon their transition from a twodimensional monolayer to three-dimensional islet-like clusters. Although clustering of these cells is commonly observed in vitro, it is not yet known whether clustering results from long-range signaling (e.g., chemotaxis) or short-range interactions (e.g., differential adhesion). To determine the mechanism behind clustering, we used experimental and computational modeling to determine the individual contributions of long-range and short-range interactions. Experimentally, the migration of PANC-1 cells on tissue culture treated plastic was tracked by time-lapse microscopy with or without a central cluster of cells that could act as a concentrated source of some long-range signal. Cell migration data was analyzed in terms of distance, number of steps, and migration rate in each direction, as well as migration rate as a function of distance from the cluster. Results did not indicate directed migration toward a central cluster (p > 0.05). Computationally, an agent-based model was used to demonstrate the plausibility of clustering by short-range interactions only. In the presence of random cell migration, this model showed that a high, but not maximal, cell-cell adhesion probability and minimal cell-substrate adhesion probability supported the greatest islet-like cluster formation.

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Section: Panc-1 Cells Do Not Exhibit Preferential Migrationsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 92%

Pancreatic Epithelial Cells Form Islet-Like Clusters in the Absence of Directed Migration

et al. 2015

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“…The MIN6 cell line displays a significant improvement in glucose induced insulin secretion when configured in pseudoislet form. 9,11,12,20,21 This has been widely attributed to enhanced cellto-cell communication and an increase in the expression of gap junction proteins that is facilitated through pseudoislet formation (Fig. 3E).…”

Section: Cell-to-cell Communication In Normal Islet Functionmentioning

confidence: 95%

“…This is particularly true of the MIN6 cell line which has been widely used for pseudoislet generation and displays significant enhancements in glucose induced insulin secretion following pseudoislet formation. [9][10][11][12] A recent NC3Rs symposium highlighted the latest advances in pseudoislet research and the usefulness of pseudoislet models to Figure 1. Glucagon and somatostatin regulate insulin release from the β-cell.…”

Section: Cellular Models Of Insulin Secretion and Pseudoisletsmentioning

confidence: 99%

Role of islet structure and cellular interactions in the control of insulin secretion

Kelly¹,

McClenaghan²,

Flatt³

2011

Islets

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“…Both pathways of communication are disrupted when the islet is dissociated into single cells as is traditionally done prior to patch-clamp characterization. The functional significance of intercellular signalling is suggested by the fact that isolated b-cells exhibit a much poorer secretory capacity than b-cells in the intact islet (Pipeleers et al 1982;Luther et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Cell coupling in mouse pancreatic β-cells measured in intact islets of Langerhans

Zhang

Galvanovskis

Abdulkader

et al. 2008

Phil. Trans. R. Soc. A.

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The perforated whole-cell configuration of the patch-clamp technique was applied to functionally identified b-cells in intact mouse pancreatic islets to study the extent of cell coupling between adjacent b-cells. Using a combination of current-and voltage-clamp recordings, the total gap junctional conductance between b-cells in an islet was estimated to be 1.22 nS. The analysis of the current waveforms in a voltage-clamped cell (due to the firing of an action potential in a neighbouring cell) suggested that the gap junctional conductance between a pair of b-cells was 0.17 nS. Subthreshold voltage-clamp depolarization (to K55 mV) gave rise to a slow capacitive current indicative of coupling between b-cells, but not in non-b-cells, with a time constant of 13.5 ms and a total charge movement of 0.2 pC. Our data suggest that a superficial b-cell in an islet is in electrical contact with six to seven other b-cells. No evidence for dye coupling was obtained when cells were dialysed with Lucifer yellow even when electrical coupling was apparent. The correction of the measured resting conductance for the contribution of the gap junctional conductance indicated that the whole-cell K ATP channel conductance (G K,ATP ) falls from approximately 2.5 nS in the absence of glucose to 0.1 nS at 15 mM glucose with an estimated IC 50 of approximately 4 mM. Theoretical considerations indicate that the coupling between b-cells within the islet is sufficient to allow propagation of [Ca 2C ] i waves to spread with a speed of approximately 80 mm s K1 , similar to that observed experimentally in confocal [Ca 2C ] i imaging.

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MIN6 β-cell–β-cell interactions influence insulin secretory responses to nutrients and non-nutrients

Cited by 87 publications

References 41 publications

Pancreatic Epithelial Cells Form Islet-Like Clusters in the Absence of Directed Migration

Pancreatic Epithelial Cells Form Islet-Like Clusters in the Absence of Directed Migration

Role of islet structure and cellular interactions in the control of insulin secretion

Cell coupling in mouse pancreatic β-cells measured in intact islets of Langerhans

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