Oscillations
in
insulin
secretion,
driven
by
islet
Ca
2+
waves,
are
crucial
for
glycemic
control.
Prior
studies,
performed
with
single-plane
imaging,
suggest
that
subpopulations
of
electrically
coupled
β-cells
have
privileged
roles
leading
and
coordinating
the
propagation
waves.
Here,
we
used
3D
light-sheet
imaging
to
analyze
location
activity
single
within
entire
at
>2
Hz.
In
contrast
network
analysis
indicates
most
highly
synchronized
located
center,
remain
regionally
but
not
cellularly
stable
between
oscillations.
This
subpopulation,
which
includes
‘hub
cells’,
is
insensitive
changes
fuel
metabolism
induced
glucokinase
pyruvate
kinase
activation.
initiate
wave
(‘leaders’)
periphery,
strikingly,
change
their
identity
over
time
via
rotations
axis.
Glucokinase
activation,
increased
oscillation
period,
reinforced
leader
cells
stabilized
Pyruvate
despite
increasing
frequency,
had
no
effect
on
cells,
indicating
origin
patterned
input.
These
findings
emphasize
stochastic
nature
β-cell
control
oscillations
identify
a
role
spatially
patterning
‘leader’
β-cells.
Biophysical Journal,
Journal Year:
2023,
Volume and Issue:
122(5), P. 784 - 801
Published: Feb. 2, 2023
Islets
of
Langerhans
operate
as
multicellular
networks
in
which
several
hundred
β
cells
work
synchrony
to
produce
secretory
pulses
insulin,
a
hormone
crucial
for
controlling
metabolic
homeostasis.
Their
collective
rhythmic
activity
is
facilitated
by
gap
junctional
coupling
and
affected
their
functional
heterogeneity,
but
the
details
this
robust
coordinated
behavior
are
still
not
fully
understood.
Recent
advances
imaging
optogenetic
photopharmacological
strategies,
well
network
science,
have
led
discovery
specialized
cell
subpopulations
that
were
suggested
critically
determine
dynamics
islets.
In
particular
hubs,
i.e.,
with
many
connections,
believed
significantly
enhance
communication
capacities
intercellular
facilitate
an
efficient
spreading
Ca
PLoS Computational Biology,
Journal Year:
2024,
Volume and Issue:
20(5), P. e1012130 - e1012130
Published: May 13, 2024
Within
the
islets
of
Langerhans,
beta
cells
orchestrate
synchronized
insulin
secretion,
a
pivotal
aspect
metabolic
homeostasis.
Despite
inherent
heterogeneity
and
multimodal
activity
individual
cells,
intercellular
coupling
acts
as
homogenizing
force,
enabling
coordinated
responses
through
propagation
waves.
Disruptions
in
this
coordination
are
implicated
irregular
hallmark
diabetes.
Recently,
innovative
approaches,
such
integrating
multicellular
calcium
imaging
with
network
analysis,
have
emerged
for
quantitative
assessment
cellular
islets.
However,
different
groups
use
distinct
experimental
preparations,
microscopic
techniques,
apply
methods
to
process
measured
signals
various
derive
functional
connectivity
patterns.
This
makes
comparisons
between
findings
their
integration
into
bigger
picture
difficult
has
led
disputes
interpretations.
To
address
these
issues,
we
present
here
systematic
analysis
how
approaches
influence
representation
islet
activity.
Our
show
that
choice
used
construct
networks
is
not
crucial,
although
care
needed
when
combining
data
from
Conversely,
conclusions
drawn
can
be
heavily
affected
by
pre-processing
time
series,
type
oscillatory
component
signals,
preparation.
tutorial-like
investigation
aims
resolve
interpretational
reconcile
conflicting
views,
advance
implications,
encourage
researchers
adopt
analysis.
As
conclude,
outline
challenges
future
research,
emphasizing
broader
applicability
our
other
tissues
exhibiting
complex
dynamics.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 26, 2024
Calcium
imaging
enables
real-time
recording
of
cellular
activity
across
various
biological
contexts.
To
assess
the
individual
cells,
scientists
typically
manually
outline
cells
based
on
visual
inspection.
This
manual
cell
masking
introduces
potential
user
error.
ameliorate
this
error,
we
developed
Correlation-Refined
Image
Segmentation
Process
(CRISP),
a
two-part
automated
algorithm
designed
to
both
enhance
accuracy
user-drawn
masks
and
automatically
identify
masks.
We
tested
CRISP
calcium
images
densely
packed
β-cells
within
islet
Langerhans.
Because
these
are
islet,
traditional
clustering-based
image
segmentation
methods
struggle
outlines.
Using
isolated
from
two
different
mouse
phenotypes
imaged
confocal
microscopes,
show
that
is
generalizable
accurate.
test
benefit
using
in
functional
analyses,
improves
network
analysis
utilize
characterize
distribution
β-cell
size.
Diabetes
is
caused
by
the
inability
of
electrically
coupled,
functionally
heterogeneous
β-cells
within
pancreatic
islet
to
provide
adequate
insulin
secretion.
Functional
networks
have
been
used
represent
synchronized
oscillatory
[Ca2+]
dynamics
and
study
β-cell
subpopulations,
which
play
an
important
role
in
driving
function.
The
mechanism
highly
subpopulations
drive
function
unclear.
We
experimental
computational
techniques
investigate
relationship
between
functional
networks,
structural
(gap
junction)
intrinsic
slow
fast
oscillating
islets.
Highly
network
were
differentiated
dynamics,
including
metabolic
activity
KATP
channel
conductance,
more
than
coupling.
Consistent
with
this,
predictive
high
synchronization
as
compared
levels
Finally,
dysfunction
gap
junctions,
can
occur
diabetes,
decreases
efficiency
clustering
network.
These
results
indicate
that
rather
structure
connections
but
junctions
are
still
essential
for
overall
efficiency.
findings
deepen
our
interpretation
formation
dynamic
tissues
such
islet.
Oscillations
in
insulin
secretion,
driven
by
islet
Ca
2+
waves,
are
crucial
for
glycemic
control.
Prior
studies,
performed
with
single-plane
imaging,
suggest
that
subpopulations
of
electrically
coupled
β-cells
have
privileged
roles
leading
and
coordinating
the
propagation
waves.
Here,
we
used
3D
light-
sheet
imaging
to
analyze
location
activity
single
within
entire
at
>2
Hz.
In
contrast
network
analysis
indicates
most
highly
synchronized
located
center,
remain
regionally
but
not
cellularly
stable
between
oscillations.
This
subpopulation,
which
includes
‘hub
cells’,
is
insensitive
changes
fuel
metabolism
induced
glucokinase
pyruvate
kinase
activation.
initiate
wave
(‘leaders’)
periphery,
strikingly,
change
their
identity
over
time
via
rotations
axis.
Glucokinase
activation,
increased
oscillation
period,
reinforced
leader
cells
stabilized
Pyruvate
despite
increasing
frequency,
had
no
effect
on
cells,
indicating
origin
patterned
input.
These
findings
emphasize
stochastic
nature
β-cell
control
oscillations
identify
a
role
spatially
patterning
‘leader’
β-cells.
Oscillations
in
insulin
secretion,
driven
by
islet
Ca
2+
waves,
are
crucial
for
glycemic
control.
Prior
studies,
performed
with
single-plane
imaging,
suggest
that
subpopulations
of
electrically
coupled
β-cells
have
privileged
roles
leading
and
coordinating
the
propagation
waves.
Here,
we
used
three-dimensional
(3D)
light-sheet
imaging
to
analyze
location
activity
single
within
entire
at
>2
Hz.
In
contrast
3D
network
analysis
indicates
most
highly
synchronized
located
center,
remain
regionally
but
not
cellularly
stable
between
oscillations.
This
subpopulation,
which
includes
‘hub
cells’,
is
insensitive
changes
fuel
metabolism
induced
glucokinase
pyruvate
kinase
activation.
β-Cells
initiate
wave
(leaders)
periphery,
strikingly,
change
their
identity
over
time
via
rotations
axis.
Glucokinase
activation,
increased
oscillation
period,
reinforced
leader
cells
stabilized
Pyruvate
despite
increasing
frequency,
had
no
effect
on
cells,
indicating
origin
patterned
input.
These
findings
emphasize
stochastic
nature
β-cell
control
oscillations
identify
a
role
spatially
patterning
‘leader’
β-cells.
Scientific Reports,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: March 3, 2025
A
novel
global
cooperative
phenomenon
was
observed
in
monolayers
of
HeLa
cervical
cancer
cells
that
exhibited
glycolytic
oscillations
but
did
not
exhibit
synchronisation
or
partial
synchronisation.
The
analysis
causality
the
between
cell
pairs
cell-monolayer
sheet
revealed
a
hidden
causal
interaction
network.
Furthermore,
network
exhibits
characteristics
broad-scale
This
suggests
key
perform
hub-like
function
and
population
forms
metabolically
connected
functional
rather
than
randomly
one.
Unlike
previous
work
focused
on
cells,
present
study
analysed
oscillating
by
Convergent
Cross
Mapping
(CCM),
which
is
based
phase-space
reconstruction
time-series
data
used
to
find
weakly
coupled
components
nonlinear
dynamical
systems.
We
believe
framework
proposed
this
useful
for
investigating
state
group
can
accelerate
studies
cellular
metabolic
phenomena
including
$$\:\beta\:$$
within
islets
Langerhans.
It
would
also
be
applicable
systems
oscillators
may
include
phenomena.