For the first time, scientists have discovered that pancreatic cell ciliary swings control insulin release

Jing Hughes, an endocrinologist at Washington University in St.
Louis, worked late in the lab to image
cilia in mouse pancreatic β cells.
These cilia are tiny hair-like organelles that are thought to be static sensors that help the pancreas manage blood sugar levels, but in general, non-moving cilia are less
characteristic than their wobbly, moving cilia.
Therefore, Hughes' goal is to observe and record the distribution
of these "primary" cilia in well-defined cell masses (called islets) in organs.
Then she saw one of them moving
.

Hughes said: "At first I didn't believe it
.
She explained that she worked late into the microscope, so "I guess I'm just tired
.
" These things should not be moved
.
Hughes and his colleagues imaged pancreatic cilia under many different conditions out of curiosity, repeatedly observing the same movements, the team reported
in the Sept.
23 issue of Nature.
The study marks the first time scientists have proposed that pancreatic cilia — virtually any primary cilia — can move
due to forces generated within the structure.
Hughes said this active movement also plays an important role
in regulating insulin secretion.

The findings shocked the scientific community
.
The team's careful examination of the organelles revealed that they are a mixture between primary cilia and motor cilia, both in terms of molecules and structure, upending the long-standing binary classification
of cilia.
"We received objections from commenters.
.
.
.
.
Many of them challenge us to really defend our definition of this hybrid cilia, (asking) 'How do you know this isn't an accident?' She added
.
Ron Orbach, a biologist at Yale University who was not involved in the study, admits he was surprised too
.
"You have apples, you have oranges
.
These are two different things
.
But now we see that there is something in between
.
”

After her late-night observation, Hughes and colleagues began their study to image
primary cilia in human and mouse islets.
Each cilia is usually organized in a specific arrangement called "9+0", in which 9 pairs of fused microtubules form a hollow cylinder
.
However, to the scientists' surprise again, the cilia on the pancreatic cells deviated from this expected arrangement, which has eight external microtubule twin bodies and a central microtubule twin or monocyte
.

The researchers also used immunofluorescence microscopy to observe proteins
on live β cells.
They observed that cilia contain motor proteins, responsible for the active movement of so-called motor cilia, a known oscillation observed
only in the lungs, middle ear and respiratory tract.
"It's another big surprise
.
We thought we might be able to find one or two (motor proteins
).
We actually found an entire group," Hughes said
.

When Hughes and her team knocked out these proteins by targeting gene deletions, the movement of cilia β cells stopped
.
When the team exposed β cells lacking in motor protein to a dose of glucose to trigger insulin secretion, they observed that a key step in the response—calcium inflow—was delayed
.
This shows the researchers that motor proteins are necessary for the movement of cilia, and that these organelles do not move
passively depending on the flow of the surrounding fluid.
Instead, they studied a previously unknown cilia that not only senses the environment, but also responds
to it by regulating the function of β cells.

While there is more work to be done to figure out how the structural arrangement of this new cilia regulates its movement, he says the study opens many new doors
for us.

Hughes was equally excited
.
Her team is currently focused on further demonstrating the function
of ciliary motility in live animal models.
"I think that as in every area, a lot of work is needed to build momentum that proves or overturns dogma.
.
.
.
.
I hope that many colleagues will join forces and start working on this issue
.
”

Islet primary cilia motility controls insulin secretion