Intercellular Ca<sup>2+</sup> waves sustain coordinate insulin secretion in pig islets of Langerhans

Bertuzzi, Federico; Zacchetti, Daniele; Berra, C; Socci, C.; Pozza, G.; Pontiroli, Antonio E.; Grohovaz, Fabio

doi:10.1016/0014-5793(95)01422-5

Cited by 28 publications

(15 citation statements)

References 20 publications

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“…However, it is worth noting that we did not find major differences between fresh and cultured islets in this study. The situation in mouse islets appears to resemble that of human and pig islets, which have been consistently shown to oscillate in response to 11-16.7 mmol/l glucose (31)(32)(33). Other parameters of ␤-cell function have been reported to exhibit marked interspecies differences.…”

Section: Discussionmentioning

confidence: 86%

Differential patterns of glucose-induced electrical activity and intracellular calcium responses in single mouse and rat pancreatic islets.

et al. 2000

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Although isolated rat islets are widely used to study in vitro insulin secretion and the underlying metabolic and ionic processes, knowledge on the properties of glucose-induced electrical activity (GIEA), a key step in glucose-response coupling, has been gathered almost exclusively from microdissected mouse islets. Using a modified intracellular recording technique, we have now compared the patterns of GIEA in collagenase-isolated rat and mouse islets. Resting membrane potentials of rat and mouse ␤-cells were approximately -50 and -60 mV, respectively. Both rat and mouse ␤-cells displayed prompt membrane depolarizations in response to glucose. However, whereas the latter exhibited a bursting pattern consisting of alternating hyperpolarized and depolarized active phases, rat ␤-cells fired action potentials from a nonoscillating membrane potential at all glucose concentrations (8.4-22.0 mmol/l). This was mirrored by changes in the intracellular Ca 2+ concentration ([Ca 2+ ] i ), which was oscillatory in mouse and nonoscillatory in rat islets. Stimulated rat ␤-cells were strongly hyperpolarized by diazoxide, an activator of ATP-dependent K + channels. Glucose evoked dosedependent depolarizations and [Ca 2+ ] i increases in both rat (EC 50 5.9-6.9 mmol/l) and mouse islets (EC 50 8.3-9.5 mmol/l), although it did not affect the burst plateau potential in the latter case. We conclude that there are important differences between ␤-cells from both species with respect to early steps in the stimulussecretion coupling cascade based on the following findings: 1) mouse ␤-cells have a larger resting K + conductance in 2 mmol/l glucose, 2) rat ␤-cells lack the compensatory mechanism responsible for generating membrane potential oscillations and holding the depolarized plateau potential in mouse ␤-cells, and 3) the electrical and [Ca 2+ ] i dose-response curves in rat ␤-cells are shifted toward lower glucose concentrations. Exploring the molecular basis of these differences may clarify several a priori assumptions on the electrophysiological properties of rat ␤-cells, which could foster the development of new working models of pancreatic ␤-cell function.

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Section: Discussionmentioning

confidence: 86%

Differential patterns of glucose-induced electrical activity and intracellular calcium responses in single mouse and rat pancreatic islets.

et al. 2000

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“…(1991) and Gylfe et al (1991) also reported no asynchrony, although when improving the time resolution by reducing sampling rate the authors observed phase lags of 1-2 s in oscillations at different regions of the islet. Only recently were calcium waves in the islets of Langerhans documented (Cao et al, 1997;Bertuzzi et al, 1996Bertuzzi et al, , 1999.…”

Section: Methodsmentioning

confidence: 99%

“…On the other hand, some results (Cao et al, 1997;Bertuzzi et al, 1996Bertuzzi et al, , 1999 show that calcium waves in the islets do not require gap junction coupling between the cells and cannot have an electric nature. Thus, at least two pathways for wave propagation exist in the islets: an APpropagation-based mechanism, dependent on the presence of gap junctions between ␤-cells and another one based on the spread of some diffusible intercellular mediators.…”

Section: Propagation Mechanismsmentioning

confidence: 99%

Excitation Wave Propagation as a Possible Mechanism for Signal Transmission in Pancreatic Islets of Langerhans

Aslanidi

Mornev

Skyggebjerg

et al. 2001

Biophysical Journal

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In response to glucose application, beta-cells forming pancreatic islets of Langerhans start bursting oscillations of the membrane potential and intracellular calcium concentration, inducing insulin secretion by the cells. Until recently, it has been assumed that the bursting activity of beta-cells in a single islet of Langerhans is synchronized across the whole islet due to coupling between the cells. However, time delays of several seconds in the activity of distant cells are usually observed in the islets of Langerhans, indicating that electrical/calcium wave propagation through the islets can occur. This work presents both experimental and theoretical evidence for wave propagation in the islets of Langerhans. Experiments with Fura-2 fluorescence monitoring of spatiotemporal calcium dynamics in the islets have clearly shown such wave propagation. Furthermore, numerical simulations of the model describing a cluster of electrically coupled beta-cells have supported our view that the experimentally observed calcium waves are due to electric pulses propagating through the cluster. This point of view is also supported by independent experimental results. Based on the model equations, an approximate analytical expression for the wave velocity is introduced, indicating which parameters can alter the velocity. We point to the possible role of the observed waves as signals controlling the insulin secretion inside the islets of Langerhans, in particular, in the regions that cannot be reached by any external stimuli such as high glucose concentration outside the islets.

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“…Several studies, however, reported low insulin secretion from isolated adult pig islets [29,36,[40][41][42][43][44][45][46][47]. In vitro, on addition of glucose alone, adult pig islets secreted approximately 10 times less insulin than did human islets [48], but the insulin secretory response to glucose was improved by a cyclic adenosine monophosphate-raising agent (stimulation index of $12).…”

Section: Tools and Sources For Translation Into Clinical Practicementioning

confidence: 98%

Pig islets for clinical islet xenotransplantation

Dufrane

Gianello²

2009

Current Opinion in Nephrology and Hypertension

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Intercellular Ca²⁺ waves sustain coordinate insulin secretion in pig islets of Langerhans

Cited by 28 publications

References 20 publications

Differential patterns of glucose-induced electrical activity and intracellular calcium responses in single mouse and rat pancreatic islets.

Differential patterns of glucose-induced electrical activity and intracellular calcium responses in single mouse and rat pancreatic islets.

Excitation Wave Propagation as a Possible Mechanism for Signal Transmission in Pancreatic Islets of Langerhans

Pig islets for clinical islet xenotransplantation

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Intercellular Ca2+ waves sustain coordinate insulin secretion in pig islets of Langerhans

Cited by 28 publications

References 20 publications

Differential patterns of glucose-induced electrical activity and intracellular calcium responses in single mouse and rat pancreatic islets.

Differential patterns of glucose-induced electrical activity and intracellular calcium responses in single mouse and rat pancreatic islets.

Excitation Wave Propagation as a Possible Mechanism for Signal Transmission in Pancreatic Islets of Langerhans

Pig islets for clinical islet xenotransplantation

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Product

Resources

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Intercellular Ca²⁺ waves sustain coordinate insulin secretion in pig islets of Langerhans