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. 2017 Jun 29;9(6):109–139. doi: 10.1080/19382014.2017.1342022

Table 3.

Patterns of [Ca2+]C oscillations in human β cells.

Study Tissue Recording Stimulus Response Synchronicity
Kindmark et al., FEBS Lett 1991 161 i) isolated islets (3 patients with normal glc tolerance, Whipple´s resection, minced tissue, collagenase, cultured 1–4 d in RPMI 1640 (11,1 mM glc)
ii) insulinoma cells, (1 patient)
Fura-2 (340/380 - 515) Spectrofluoro-meter (fr = 1 Hz) glc (3→11; 0→10 / 20)
K+ (25 mM)
tolbutamide
ATP
Diazoxide
Only islets with an increase in Ca2+ considered successful (> 50% of all): i) decrease, then increase with stable (1 islet) or »fluctuating« (1 islet) plateau; ii) no initial decrease, plateau with irregular oscillations (period 70–80 s) (1 islet). n.a.
Misler et al., Diabetes 1992 122 Isolated islets (non-diabetic life supported cadavers, age and gender unknown (collagenase + Ficoll gradient), cultured 1–7 d in 5,5 mM glc Fura-2 (340/380 - 505)
spectrofluorometry (fr unknown)
perofrated patch-clamp
glc (3→10→20) i) no response to glc with subsequent response to tolbutamide (4/11 islets); ii) oscillations superimposed on a plateau (4/11); iii) slow rise to a plateau without oscillations (2/11); iv) short transients on an unchanging baseline, coalescing to a spike. n.a.
Kindmark et al., Diabetologia 1994 224 Isolated islets (9 patients, normal, impaired, and diabetic tolerance, f and m, 57–83 y (mean 65,0 yr) minced pancreas tissue, collagenase, cultured 1–4 d (in 11 mM glc) Fura-2
(340/380 - > 510)
spectrofluorometry (fr = 1 Hz)
perforated patch-clamp
glc (3→10 / 12; 15 mM for electrophysiology,
tolbutamide (100 μM)
i) fairly regular slow oscillations in both glc and tolbutamide (period = 2–3 min); ii) in some a monophasic increase continuous firing of APs (5-6 Hz), no bursts. n.a.
Hellman et al., Diabetologia 1994 225 i) isolated cells,
ii) clusters,
iii) isolated islets (8 cadaveric donors, 39 ± 5 yr, gender unknown, ductal distension and Ficoll gradient, cultured 3–7 d in 6,1 mM glc, sent by air and stored for another 1–3 d in 5,6 mM glc)
Fura-2, Indo-1
PMT or video camera, fr unknown
glc (3→20 glc, 3→3+1mM tolbutamide, 1 mM tolbutamide+20 mM glc, addition of glucagon (10 nM or glycine (10 mM)
in isolated islets glc 3→20
In isolated cells and clusters large amplitude oscillations from the basal level, fr = 0,1-0,5/min (type a) and superimposed on an elevated Ca (type b), slow oscillations were also present in tolbutamide, glucagon and glycine transformed type a to a plateau.
In islets plateau with superimposed oscillations (period 2–5 min).
Analyzed in clusters, well synchronized slow oscillations, no pacemakers.
In isolated islets well synchronized, different amplitudes, no quantification of synchronization.
Good overlap with type a oscillations and insulin release.
Higher glucose affected amplitude, not frequencies.
In isolated islets, tybe b pulses of insulin wered described (but not Ca).
Martin et al., Cell Calcium 1996 201 Isolated islets 2 cadaveric donors (age unknown) and 2 patients (44 and 80 yr),
Tissue minced and collagenase, hand picking, cultured overnight in 5,5 mM glc
Fura-2 (340/380-510)
CCD camera, fr. = 0,167 Hz)
glc 3→11, 11→16,7;
tolbutamide 50 μM
A triphasic response (31/42 islets), decrease, a rapid transient increase, then oscillations (fr. = 1 ± 0,3/min), or (11/41 islets), slow rise to a plateau w.o. osc.;
Upon elevating glc, prolonged duration or slow oscillations (0,15 ± 0,2/min) (14/17) or plateau (3/17). Tol: reversible plateau-like increase (7/7).
Synchrony in all 3 phases in all regions of an islet (13/15 islets) or regions 10–15 s out of phase (2/15).
Cabrera et al., PNAS 2006 198 Isolated islets (5 cadaveric donors, 48 ± 7 y of age), liberase + purification, cultured in CMRL (5,5 mM glc) Fura-2 (340/380-510)
CCD camera, fr. unknown.
glc 3→11 mM No general oscillatory responses (> 70 islets from 10 preparations), only localized oscillations (single cells or clusters). In dispersed cells, slow oscillations were observed, period = 5min (not further quantified). Not quantified in detail, qualitatively assessed that there is no sync.
Quesada et al., Diabetes 2006 200 Isolated islets (5 cadaveric donors (22,6 ± 5,3 yr, gender unknown; minced pancreas tissue, then collagenase, recorded acutely) Fluo-3 (488/505-530)
Ca2+ Confocal microscopy at the equatorial plane (t = 8 μm, fr = 0,5-0,25 Hz
glc via perifusion, 3→11, 11→16,7 6/41 β cells (10 islets): sustained increase without oscillations
35/41 β cells: oscillations in 11 mM (0,45 ± 0,02 /min)
Assessed qualitatively, in clusters only, sometimes more widely distributed after several minutes (4/7 islets) or a more general but weak coupling (3/7 islets). Heterogeneity in the degree of coupling, even from the same preparation.
Hodson et al. J Clin Invest 2013 56 Isolated islets (21 normoglycemic donors, isolation centers (UK, I, CH), cultured in RPMI in 5,5 mM glc Spinning-disk confocal; Fluo-2 (491-525/25) CCD, fr = 0,5 Hz glc 3→11
GLP-1 (20 nM)
Stochastic fast oscillations, large deflections in a subpopulation of β cells upon GLP-1. Moderate correlation in 11 mM glc, large synchronous deflections in Ca upon GLP-1.
De Marchi et al., J Biol Chem 2014 54 Isolated islets (2 donors, purchased (Tebu-bio), cultured in RPMI in 5,5 mM glc Genetically encoded cameleon sensor YC3.6cyto (430 - 480/40 and 535/30), CCD, fr = 0,5 Hz glc via perifusion, 1→16,7 mM, inhibition by oligomycin (2,5 μg/ml) and diazoxide (100 μM) Transient increase, then stable plateau with occasional superimposed »spikes." n.a.
Johnston et al. Cell Metab 2016 186 Isolated islets (from distant isolation centers (I, CH), cultured in RPMI in 5,5 mM glc Spinning-disk confocal; Fluo-2 (491-525/25) CCD, fr = 2-8 Hz glc 3→11 Not shown. Complex network theory analyses. Similar topological characteristics as mouse islets, more clustered/compartmentalized synchrony.
Farnsworth et al. J Biol Chem 2016 138 Isolated islets (from distant isolation centers (I, CH), cultured in RPMI in 5,5 mM glc Wide field microscope; Fluo-4 (490/40-525/36) CCD, fr = 1 Hz glc 11 Not shown. Percentage area synchronized ≈90% in controls.