Beyond the Beta Cell: Research, Regulation, and the Future of Metabolic Research at UC Davis
“Dad, what are you doing? Don’t eat that. It’s too late.” This was the accusatory statement I shot across the kitchen at 10:45 PM one night as I was typing away at my computer. I had been getting myself organized for winter quarter during break and stayed up late with my work at the kitchen counter. My dad closed the fridge, holding some chocolate pie in one hand and a cookie in the other.
“Eh, Koñcōntu tāṉ,” he replied nonchalantly. “Only a little bit.”
“You’re going to spike your blood sugar. And it’s already late,” I protested vehemently. He merely grabbed a glass of water and, content with his decisions, gathered his things to enjoy his treats in front of the television.
“It’s fine. I’m already old. I should enjoy.”
“You’re pre-diabetic. Doctor said so.”
“In 10-12 years, they will make stem cells that make insulin, and I’ll be all good to go,” he purported before meandering his way out of the kitchen and away from my judgment. At the time, I was surprised that he knew enough about science and physiology to make such a statement, but also perturbed that this knowledge was limited and he had grossly misplaced his confidence. Like my father, many Americans today lack a clear understanding of metabolism and the basic processes that underlie blood glucose regulation in our bodies; as is evidenced by the fact that 61% of Americans think blood glucose is high only after 200 mg/dL, and 56% think that their doctor will cure their diabetes [1]. In fact, 26% of the US population (8.6 million) has undiagnosed diabetes, and 38% of US adults (96 million) are prediabetic and are not aware [2]. It is one of the most important metabolic processes that helps to sustain us and provides us with energy to live freely, yet it is widely misunderstood. Understanding how blood sugar is regulated — and how it can go awry — is not as simple as watching insulin levels rise and fall. The body’s ability to balance blood glucose and metabolism relies on the constant communication between hormone-signaling cells. That is the exact focus of Dr. Mark Huising’s lab at UC Davis: the silent signals exchanged between the stars of the show - insulin-producing beta cells - and their lesser-known neighbors - the delta cells.
What Happens In the Islet Doesn't Stay In the Islet
The pancreas serves as the hub of regulation for this remarkably complex and finely tuned system of metabolic regulation. At its core are the islets of Langerhans — a cluster of specialized cells that secrete signaling hormones responsible for managing glucose levels. Among them are three primary cell types: alpha cells, beta cells, and delta cells. Beta cells secrete insulin, which enables glucose uptake into somatic cells, such as muscle and fat. When insulin levels are too low, glucose remains elevated, which can lead to serious complications like diabetic ketoacidosis, a complication of diabetes when insufficient insulin causes fats to be broken down into ketones, making the blood more acidic. Alpha cells, on the other hand, release glucagon, which raises the blood sugar by triggering glycogen breakdown in the liver and stimulating gluconeogenesis during times of low glucose availability. These are two hormones that are part of the tug-of-war that dynamically regulates glucose, but that is only half of the story. What about the delta cell? Are insulin and glucagon the only signaling hormones at play in this beautifully interwoven feedback pathway? Each discovery in metabolism research complicates, yet enriches, our understanding of this fundamental physiology.
While alpha and beta cells have largely dominated popular conversation in the scientific community about metabolism and diabetes, delta cells are equally essential in moderating the system. These cells release somatostatin, a hormone that inhibits both insulin and glucagon release, acting as a local “brake” within the islet, preventing overshooting in either direction, whether the blood glucose is too high or too low. Urocortin 3 (Ucn3) is a neuropeptide that belongs to the same family as corticotropin-releasing factor (CRF), a hormone associated with the body’s stress response, and was the subject of research by the Huising lab [3]. Dr. Mark Huising’s lab has identified Ucn3 as a key regulator in the islet, as it is co-released with insulin from beta cells, stimulating somatostatin secretion in the neighboring delta cells [4]. This feedback loop allows for controlled insulin output in response to high glucose levels that could prevent dangerous overshoots in insulin delivery. In an interview with Dr. Huising about this particular research, he explained that “insulin is one of the most dangerous drugs we give,” and emphasized that delta cell signaling provides an essential safeguard, ensuring that insulin is delivered in just the right amount at just the right time [5]. I asked Dr. Huising whether he thought the importance of the underappreciated delta cell was paramount to a future in diabetes research. We need not look far for the answer, as our conversation and his lab’s findings have already opened doors for targeting “islet crosstalk” in future studies [4].
From Bench to Bedside
But how does all this talk of peptide molecules and feedback mechanisms find its roots back in clinical applications? While the Huising lab may seem rooted in very specific biochemical pathways, its implications in the macroscopic perspective of physiology are great. The finding that delta cells are crucial in the restraint of insulin secretion is relevant in the context of diabetic therapies. Dr. Huising pointed out in our interview, “we give this drug to patients to self-medicate… and we should because they can sense their own bodies — but that comes with a risk” [5]. Insulin overdose is a real problem in medicating diabetics, especially those with type 1 diabetes. Too much insulin can cause blood sugar to drop dangerously low, depriving the brain of the glucose it needs to function and potentially leading to life-threatening consequences. Currently, there are few interventions for such overdoses, except the use of IV dextrose interventions and/or possible glucagon injections in extreme cases [6]. Studies like those of the Ucn3 molecule can help us discover further clinical solutions for these ongoing issues. The body’s own delta cells help mitigate that risk by releasing somatostatin in response to Ucn3, ensuring insulin doesn’t overshoot [4].
Methodology is equally important in the realm of research as the results themselves. Measuring peptides such as Ucn3, which are found in low abundance, meant engineering specialized mouse models to study these signalling pathways. The lab had to perform islet isolations by injecting collagenase (an enzyme that breaks down structural protein in tissue) into the mouse pancreas and then removing them for further cell analysis. A clear theme across many of the Huising lab’s publications is a strict adherence to reproducibility. This commitment to patience and precision in gathering results is what distinguishes this lab and allows it to reliably place one stone at a time in the wall of complex physiology, instead of rushing to throw together an incomplete narrative. I asked Dr. Huising if such a process could be tedious or frustrating. He replied that in the matter of reproducibility, if you aren’t getting the right results again, then you aren’t asking the right questions [5].
In looking back on the many publications with Huising’s involvement, one piqued my interest and immediately made me think of my father’s confident assertion that one day he would, in fact, not have to worry about his late-night sweet treats. In a 2021 study, the lab had explored the chromatin availability of alpha and delta cells and found that their genomes were readily “poised” or primed for a beta-like identity. This meant that there is a possible plasticity to islet cells that could allow us to use molecular cues to induce certain existing cells to turn into different cell types — essentially reprogramming the cell [7]. Dr. Huising made it clear in our interview, though, that these results were observed in low frequency and there are still many more questions to be answered regarding the safety and efficiency of applying this in a clinical setting. As for the stem-cell therapies, local devices made to carry transplant stem cells that turn into beta cells are still under heavy scrutiny. Dr. Huising warned that those devices need to be engineered in a way that prevents cell proliferation (cancer) and “dumping insulin uncontrollably” [5]. He mentioned that we are still a ways out from such treatment being the norm rather than the exception. Sorry, Dad. Still, the research opens up new possibilities and lays an educational foundation for further innovation.
The Future of Research
Despite such promising results and potential for clinical and educational applications, research like that of the Huising lab faces increasing uncertainty due to declining federal funding. In our interview, he emphasized that public institutions rely on national institutions to sustain such projects outside of the industry. Work like this isn’t just a one-off experiment or project - it’s decades-long work that builds a foundational understanding. It is work that will potentially be part of the new curriculum in schools, helps future scientists build on their knowledge, and can be used as a reference for clinical research. Dr. Huising emphasized in our conversations regarding the national cuts that they reduce opportunities for training young scientists. Many of the young researchers working and volunteering in his lab gain valuable experiences that help to propel their understanding of the scientific method and thus their careers. Without such funding, a future in foundational research is under attack, and its impacts are largely still unknown.
From the kitchen counter to the lab bench, conversations about metabolism are gaining importance in the growing market of knowledge. Dr. Huising’s lab unravels the intricate relationships that hold the key to solving some of our most pressing metabolic issues. What stands out in conversations with researchers like Dr. Huising isn’t just their depth of knowledge— it’s their passion. Their passion is to not only uncover more, but also to explore how new science can spur curiosity and integrity in the next generation of thinkers. In writing this paper, I read a draft of my ideas to my father and taught him some of the mechanisms behind the metabolic functions that he had so recently started monitoring closely. The conversation spurred his own curiosity and even inspired him to do more research of his own. When funding, policy, and public perception lag behind discovery, work like this on our campus reminds us that science is not just about breakthroughs in a lab, but the people it impacts - the very people who engage in everyday conversations about their own physiology around the kitchen counter.
Author’s Note
I wrote this piece to connect the everyday conversations about science and health to the research being done right here at UC Davis. After taking physiology with Dr. Huising, I became curious not just about insulin signaling, but also the researchers behind these metabolic discoveries, especially given my own family's experience with diabetes. That curiosity led me to interview Dr. Huising in person and learn about his lab’s work on hormone regulation. I chose to write this in my spare time because I am passionate about science communication and making complex topics more accessible. With the recent national cuts to research funding, stories like these feel especially urgent because they intersect with biology, public health, and policy. My hope is that readers come away with a deeper appreciation of why this kind of research matters, not just in the lab, but in laying the foundation for future innovation.
References
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