The researchers discovered a special group of “first responder” cells that are important for triggering a blood sugar response.

How does the human body control blood sugar levels so precisely? An international research team led by scientists from the Paul Langerhans Institute Dresden (PLID) of the German Diabetes Research Center has come one step closer to the answer. They have discovered a special group of “first responder” cells in the pancreas that are important for triggering a blood sugar response. Their findings have been published in the journal. Scientific progress.

Our bodies need to keep blood sugar levels at a healthy level; too high or too low is dangerous. In diabetes, this balance is disrupted, leading to serious health problems. Beta cells in the pancreas manage this balance by releasing insulin when blood sugar levels rise. Understanding how beta cells function and regulate their response to elevated blood sugar levels may ultimately help develop better treatments for diabetes.

“Looking at the pancreas, we wondered whether all beta cells are actually equally sensitive to glucose. Previous studies have suggested that some cells might be more sensitive than others.”

Professor Nikolai Ninov, Research Group Leader, CRTD, Dresden

To understand how the pancreas works, Ninov's team turned to zebrafish. This tiny tropical fish has a pancreas that functions similarly to the human pancreas. But it also has a major advantage: it's completely pigmented and transparent, allowing researchers to observe the functioning of a live fish's pancreas in real time.

The team found that a small population of beta cells is more sensitive to sugar levels than other cells. Because these cells respond to glucose faster than other cells, Ninov's team named them “first responder” cells. These cells initiate the glucose response, and the rest of the “follower cells” follow suit.

The team wanted to test whether first responders were necessary for follow-on cells to respond to glucose. Using transparent fish, the Ninov group took advantage of optogenetics, a cutting-edge light-based technology that can turn individual cells on or off with light rays. Turning off first responder cells reduced the follow-on cells' response to blood sugar. At the same time, selective activation of first responders enhanced the response of follow-on cells.

“First responders are at the top of the beta cell hierarchy in terms of controlling the response to sugar. Interestingly, only about 10% of beta cells act as first responders, suggesting that this small population of cells acts as a control centre that regulates the activity of the remaining beta cells,” explains Professor Ninov.

To characterize the first responder cells, the researchers compared gene expression in glucose-sensitive beta cells with less sensitive beta cells. They found that first responder cells are involved in the production of vitamin B6. First responder cells express a key enzyme that converts the inactive form of vitamin B6 in the diet into its active form inside the cells. Working closely with Professor Guy Rutter's team at the University of Montreal, the researchers stopped the production of vitamin B6 in both zebrafish and mouse pancreases. In both species, the ability of beta cells to respond to hyperglycemia was dramatically reduced. “This indicates that vitamin B6 plays an evolutionarily conserved role in the response to glucose. It is possible that first responder cells produce vitamin B6 and supply it to the remaining beta cells to regulate their activity. One of the next steps will be to see if this is indeed the case,” says Professor Ninov.

“We know that there are certain cells that initiate a glucose response, and vitamin B6 is essential for this process,” says Professor Ninov. Vitamin B6 acts as a cofactor for over 100 essential enzymes that play key roles in cells, from controlling cellular respiration to producing neurotransmitters. “Indeed, there is a body of research showing a correlation between low levels of vitamin B6 and the incidence of metabolic diseases and type 2 diabetes. We want to focus more on investigating that connection,” concludes Professor Ninov. Understanding how vitamin B6 regulates pancreatic beta cells could provide new insights into diabetic pathology and ultimately lead to new treatments.