Recent studies have found that a special group of beta cells in the pancreas is crucial for driving blood sugar responses.
We know that pancreatic beta cells play a key role in regulating blood sugar levels, but are all beta cells equally sensitive to sugar? Dresden University of Technology To find out just this, researchers at the University of Manchester (Germany) are using the zebrafish as a model organism, hoping to gain a better understanding of beta cell function and develop better treatments for diabetes.
The ability to regulate blood glucose levels is essential to our health. When beta cells first recognize high blood glucose levels, they depolarize, causing an increase in intracellular calcium and a rapid release of insulin. The second phase of this process is a more sustained release of insulin. This ability to regulate blood glucose levels is impaired in diabetes, with people with prediabetes showing a defect in the initial insulin release and those with type 2 diabetes showing an additional defect in the second phase of insulin release.
To gain deeper insight into the function of pancreatic beta cells, the researchers turned to a transparent model organism that’s not all that different from the human organ. Zebrafish offer researchers the ability to observe the pancreas of a living fish in real time. Utilizing optogenetics — a light-based technique that switches single cells on and off with a beam of light — the research team investigated the role of individual beta cells in the glucose response, and targeted activation and inactivation of beta cells.
The researchers observed that a particular group of beta cells responded to glucose more quickly than other cells. They called this group “first responders” and the other group “follower cells.” The researchers wanted to find out whether activation of the first responders was an essential component of the glucose response of follower cells. They used optogenetics to turn off the first responder cells and observed that the follower cells subsequently reduced their glucose response. Selectively activating the first responders enhanced the response of the follower cells.
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“First responders are at the top of the beta cell hierarchy when it comes to controlling the response to sugar. Interestingly, only about 10% of beta cells act as first responders, suggesting that this small cell population acts as a control centre that regulates the activity of the remaining beta cells,” explains senior author Nikolai Ninov.
The team went a step further by genetically characterizing first responders to tease out how they differed from follower cells. By comparing gene expression in beta cells that are more sensitive to glucose with those that are less sensitive, they found that first responders express an enzyme involved in producing vitamin B6, essential for converting inactive dietary B6 into an active form that cells can use.
They found that when B6 production was stopped in first responder cells in the pancreas of both zebrafish and mice, the beta cell response to rising glucose levels was reduced. “This suggests that vitamin B6 plays an evolutionarily conserved role in the response to glucose. It could be that first responders produce vitamin B6 and supply it to the remaining beta cells to regulate their activity. One of our next steps will be to see if this is indeed the case,” Ninov reported.
Now that we know that vitamin B6 plays a key role in glucose response, researchers are interested in investigating the previously unexplored link between this vitamin and metabolic diseases and type 2 diabetes. By gaining a better understanding of beta cells and the factors involved in their proper functioning, we may be able to learn more about diabetic pathology and potential new treatments.
