Postdoc Portrait: Hannah Waterman Investigates Gap Junction Communication

Hannah Waterman is a postdoctoral researcher at Duke University. Her research focuses on understanding how communication between pancreatic alpha and beta cells regulates insulin release. In this Postdoc Portrait interview, she discusses the importance of her work and how she hopes her research will help improve diabetes treatments.

Tip 2 Diyabette Pankreas Adacık Hücresi İletişimini Çözümleme

Bu başlık, Tip 2 diyabetinde pankreas adacık hücreleri arasındaki iletişim mekanizmalarının incelenmesine işaret ediyor. Adacık hücreleri, özellikle insülin üreten beta hücreleri, kan şekerini düzenlemede kritik bir rol oynar. Bu hücreler arasındaki sinirsel, kimyasal ve moleküler iletişim, insülin salınımının uyumlu çalışmasını sağlar.

Tip 2 diyabetinde bu iletişim bozulur ve beta hücre fonksiyonları azalır. Araştırmacılar, bu iletişimin nasıl kırıldığını ve tedavi için nasıl yeniden kurulabileceğini anlamaya çalışmaktadır. Hücre içi sinyal iletimi, gap junction (ara bağlantı) iletimi ve parakrin etkileşimler bu süreçte önemli faktörlerdir.

Bu alandaki çalışmalar, yeni tedavi yaklaşımlarının geliştirilmesine yön verebilir. Pankreas adacık hücre iletişimini korumak veya iyileştirmek, diyabet yönetiminde umut verici bir hedef olarak öne çıkıyor.

S | What is the scientific problem you are trying to solve?

The fundamental scientific problem my research seeks to address is why the insulin-enhancing effects of glucose-dependent insulinotropic polypeptide (GIP)—an intestinal hormone released after meals that stimulates insulin secretion—become impaired in the early stages of type 2 diabetes, despite the preservation of GIP receptor expression and the sustained clinical efficacy of GIP receptor agonists. This suggests that the fundamental mechanisms regulating GIP’s action have not yet been clarified. While pancreatic beta cells produce insulin to lower blood sugar, neighboring alpha cells secrete glucagon to raise blood sugar and also coordinate communication within the islet. Increasing evidence indicates that amino acids, primarily alanine, activate alpha cells via GIP receptor signaling, leading to the release of factors that increase insulin secretion from beta cells. However, it remains unknown whether this nutrient-driven alpha-to-beta cell signaling pathway operates in humans. My research combines controlled human metabolism studies with experiments performed on human pancreatic islets to determine how alanine and GIP work together to regulate insulin secretion. Understanding this mechanism may explain why GIP function changes in type 2 diabetes and could help identify new approaches to improve incretin-based therapies and preserve beta cell function.

What drew you into metabolism research?

I turned to research because it has a direct impact on a disease that affects my own family and millions of people worldwide. During my undergraduate studies, I was fascinated by how precisely the body regulates blood glucose through the coordinated communication between organs and cell types. This interest led me to pursue a doctoral degree in metabolic physiology, where I investigated how prior insulin exposure alters hepatic glucose metabolism later in the day using large animal models. Through these studies, I developed a deep appreciation for integrative physiology and for studying mechanisms in systems that closely mirror human biology.

As I transitioned to my postdoctoral training, I began exploring unanswered questions regarding incretin hormones and pancreatic islet biology. In particular, despite the remarkable clinical success of GIP-based therapies, I wondered why the effect of GIP is impaired in type 2 diabetes. My research now focuses on understanding the communication between pancreatic alpha and beta cells that regulate insulin secretion, and uncovering mechanisms that could improve diabetes treatments.

Q | What did you learn from your research about something you didn’t expect?

One of the most surprising things I learned is that hormones rarely act on their own. In the early stages of my training, I viewed GIP as a hormone that directly acts on pancreatic beta cells to stimulate insulin secretion. As I began reviewing the literature and designing experiments, I realized that pancreatic alpha cells also play an active role in this process. Alpha cells don’t just secrete glucagon to raise blood sugar; they respond to nutrients such as amino acids and communicate with neighboring beta cells to enhance insulin secretion. This shift in perspective fundamentally changed how I think about metabolic regulation. It reinforced my understanding that physiology doesn’t operate through isolated, independent pathways, but rather through coordinated interactions between cells and organs. This awareness shaped my research approach, directing me toward asking more integrative questions and designing experiments that reflect the complexity of human metabolism, rather than studying individual hormones or cell types in isolation.

S | If your research is successful, what could it change for science or society?

If my research is successful, it will enhance our understanding of how the body regulates blood sugar and how these processes are disrupted in type 2 diabetes. By uncovering new mechanisms that control insulin secretion, this work may help explain why certain existing treatments are effective and identify opportunities to develop better therapies. More broadly, my research lays the foundation for future discoveries in metabolism and endocrinology by contributing to a deeper understanding of human physiology. Type 2 diabetes affects hundreds of millions of people worldwide and increases the risk of serious complications such as heart disease, kidney disease, blindness, and others, making it one of the greatest public health challenges of our time. Even small advances in our understanding of the disease hold the potential to improve patient care. I hope this research not only contributes to more effective strategies for preventing, treating, and managing diabetes but also helps nurture the next generation of scientists who will tackle these complex biomedical challenges.

Q | What is the question you’re most excited to answer next?

The question I’m most excited to answer is how the body primes itself to maintain normal blood sugar levels well before type 2 diabetes develops. The fact that many people remain metabolically healthy for years despite increasing insulin resistance suggests that there are powerful compensatory mechanisms preserving glucose homeostasis. I want to understand what these mechanisms are, why some of them fail over time in certain individuals, and whether they can be strengthened to delay or prevent the progression of the disease. Answering these questions will shift the focus from treating established diabetes to preserving metabolic health before irreversible damage occurs. The idea that studying these early adaptive responses will reveal new biological principles and create opportunities for interventions that help people stay healthy for longer—rather than simply managing the disease once it has developed—is what excites me.

The answers are organized in terms of length and clarity.