Junctional communication of pancreatic β cells contributes to the control of insulin secretion and glucose tolerance

Charollais, Anne; Gjinovci, Asllan; Huarte, Joachim; Bauquis, Juliette; Nadal, Ángel; Martı́n, Franz; Andreu, Etelvina; Sánchez-Andrés, Juan Vicente; Calabrese, Alessandra; Bosco, Domenico; Soria, Bernat; Wollheim, Claes B.; Herrera, Pedro Luis; Meda, Paolo

doi:10.1172/jci9398

Cited by 121 publications

(119 citation statements)

References 28 publications

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“…Given that a neighbouring coupled cell experiences approximately 30 per cent of the voltage applied to the voltage-clamped cells (i.e. 27 mV out of the 86 mV applied to patched cell; see above), then the membrane potential of the electrically coupled cell will change by approximately Lucifer yellow has previously been used to visualize coupling between islet cells (Meda et al 1986;Charollais et al 2000). Patch electrodes were filled with Lucifer yellow (2 mM) and the cell was imaged on a confocal microscope.…”

Section: (D ) Analysis Of Capacitive Currents In Isletsmentioning

confidence: 99%

“…In the intact pancreatic islets, intercellular signalling can occur via both chemical (paracrine; Rorsman et al 1989;Salehi et al 2005) and electrical (via gap junctions; Charollais et al 2000) signals. Both pathways of communication are disrupted when the islet is dissociated into single cells as is traditionally done prior to patch-clamp characterization.…”

Section: Introductionmentioning

confidence: 99%

“…Evidence for electrical coupling via gap junctions between islet cells has previously been provided by electron microscopy (Orci et al 1975), recordings of membrane potential and currents using sharp intracellular electrodes (Meissner 1976;Eddlestone et al 1984;Mears et al 1995), patch-clamp experiments on isolated islet cell pairs (Perez-Armendariz et al 1991) and dye coupling (Michaels & Sheridan 1981;Charollais et al 2000). It has in fact been proposed that the b-cells function as a 'secretory syncytium' (Santos et al 1991).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: (D ) Analysis Of Capacitive Currents In Isletsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…with either 0.22 mg/g of freshly prepared streptozotocin (Sigma Chemicals, St Louis, MO, USA) or the corresponding volume (15 μl/g) of the 0.1 mmol/l citrate buffer (pH 4.5) that was used to dissolve the drug. Thereafter, blood glucose levels of all animals were evaluated every 3 days using a Glucocheck [22].…”

Section: Semi-automatic Islet Detectionmentioning

confidence: 99%

“…One piece was immediately extracted in 5 ml acid ethanol for evaluation of insulin content, as determined by a radioimmunoassay [22]. The other piece was fixed for xfOCM under double-blind conditions.…”

Section: Semi-automatic Islet Detectionmentioning

confidence: 99%

In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy

et al. 2009

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Aims/hypothesis Structural and functional imaging of the islets of Langerhans and the insulin-secreting beta cells represents a significant challenge and a long-lasting objective in diabetes research. In vivo microscopy offers a valuable insight into beta cell function but has severe limitations regarding sample labelling, imaging speed and depth, and was primarily performed on isolated islets lacking native innervations and vascularisation. This article introduces extended-focus optical coherence microscopy (xfOCM) to image murine pancreatic islets in their natural environment in situ, i.e. in vivo and in a label-free condition.Methods Ex vivo measurements on excised pancreases were performed and validated by standard immunohistochemistry to investigate the structures that can be observed with xfOCM. The influence of streptozotocin on the signature of the islets was investigated in a second step. Finally, xfOCM was applied to make measurements of the murine pancreas in situ and in vivo. Results xfOCM circumvents the fundamental physical limit that trades lateral resolution for depth of field, and achieves fast volumetric imaging with high resolution in all three dimensions. It allows label-free visualisation of pancreatic lobules, ducts, blood vessels and individual islets of Langerhans ex vivo and in vivo, and detects streptozotocin-induced islet destruction. Conclusions/interpretation Our results demonstrate the potential value of xfOCM in high-resolution in vivo studies to assess islet structure and function in animal models of diabetes, aiming towards its use in longitudinal studies of diabetes progression and islet transplants.

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The source(s) for new pancreatic beta cells in adult life

Bock

2004

BioEssays

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The natural source for new pancreatic beta cells is an important issue both for understanding the pathogenesis of diabetes, and for possibly curing diabetes by increasing the number of beta cells. Dor et al. investigated beta-cell renewal and regeneration by genetic lineage analysis in mice during physiological growth and after partial pancreatectomy. The data conclusively showed that beta-cell replication was the only source for new beta cells without contributions from stem cells or other non-beta cells. This underlines the capacity for beta-cell self-renewal and casts doubt that other cell types are able to generate new beta cells in the intact pancreas.

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Junctional communication of pancreatic β cells contributes to the control of insulin secretion and glucose tolerance

Cited by 121 publications

References 28 publications

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

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

In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy

The source(s) for new pancreatic beta cells in adult life

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