HIRN Review Series in Molecular Metabolism (2021-2023)

HIRN Review Series in Molecular Metabolism (2021–2024)

Through the efforts of the HIRN Trans-Network Committee (TNC), the Human Islet Research Network (HIRN) was invited to develop a collaborative review series for Molecular Metabolism. The series brings together HIRN investigators and collaborators from across the network to examine fundamental questions in human islet and β-cell biology, the immune processes underlying type 1 diabetes (T1D), and emerging approaches to preserve, restore, and replace functional β-cell mass.

The eight reviews were developed as a collaborative effort spanning multiple scientific disciplines and areas of HIRN research. Together, they provide historical context, highlight advances in the field, identify persistent knowledge gaps and challenges, and describe emerging technologies and approaches that may enable new directions in T1D research and therapy.

The Series at a Glance

Taken together, the eight publications tell a story that moves from defining the biology of the human β cell and understanding how it is lost in T1D, to developing increasingly sophisticated models and therapeutic strategies to protect, regenerate, or replace it.

The series begins by establishing the scientific foundation for HIRN and the importance of studying human biology. From Type 1 Diabetes Biology to Therapy: The Human Islet Research Network introduces HIRN’s collaborative approach and identifies major questions surrounding human β-cell loss and the development of new therapeutic strategies. The series then turns to a fundamental question—What is a β Cell?—examining the characteristics of a mature, functional human β cell and emphasizing the need for rigorous standards when evaluating β cells and β-like cells generated through new technologies.

The next group of reviews explores the complex biology of β-cell dysfunction and immune-mediated destruction. Modeling Human T1D-associated Autoimmune Processes examines experimental approaches for studying human T1D immunobiology and the challenges of developing models that adequately reflect the heterogeneity of human disease. The Beta Cell-immune Cell Interface in Type 1 Diabetes (T1D) further examines the dynamic interactions between β cells and immune cells that contribute to disease progression. Together, these reviews underscore the importance of studying β cells within their broader cellular and immune environment rather than in isolation.

The series also highlights the increasingly important role of the islet microenvironment and intercellular communication. Extracellular Vesicles in β Cell Biology explores how extracellular vesicles and their molecular cargo contribute to communication among cells and may influence β-cell function and disease. These mechanisms complement the broader view of the pancreatic tissue ecosystem emerging across HIRN research.

A parallel theme throughout the series is the development of new human-based models and therapeutic approaches. Stem Cell-based Multi-tissue Platforms to Model Human Autoimmune Diabetes examines emerging platforms that combine stem cell biology, tissue engineering, and immune components to model human autoimmune diabetes. Emerging Diabetes Therapies: Bringing Back the Beta-cells considers approaches aimed at restoring functional β-cell mass through regeneration, replacement, and related therapeutic strategies. Together, these reviews illustrate how advances in human cell biology, stem cell technology, tissue engineering, and disease modeling are creating new opportunities to study and ultimately address T1D.

The most recent review, Untangling the Genetics of Beta Cell Dysfunction and Death in Type 1 Diabetes, extends the series into the genetic and genomic mechanisms underlying β-cell dysfunction and death. It examines how human genetic studies can connect T1D-associated variants to candidate genes and biological mechanisms, while highlighting opportunities to use genetic information to better understand disease heterogeneity and inform future therapeutic and prevention strategies.

An Integrated View of Human T1D Biology

Across all eight publications, several interconnected themes emerge: the importance of studying human β-cell biology, the need to understand β cells within their immune and tissue environments, the value of increasingly sophisticated human-based models, and the potential of integrating genetic, molecular, cellular, and functional data to address unanswered questions in T1D.

Together, the reviews demonstrate how progress in T1D research increasingly depends on connecting these areas rather than studying them independently. Defining what constitutes a healthy, functional human β cell provides a foundation for understanding β-cell dysfunction and death; understanding the interactions between β cells and immune cells informs disease modeling and therapeutic development; and advances in stem cell biology, tissue engineering, extracellular vesicle biology, and genetics provide new tools for investigating these processes and developing strategies to preserve or restore β-cell function.

The series reflects HIRN’s collaborative, cross-disciplinary approach to addressing the complex biology of T1D and highlights both the progress made and the scientific challenges that remain. Collectively, the eight reviews provide a resource for the broader research community and a framework for identifying important questions and opportunities for future investigation.

A link to the virtual digital collection is available HERE and below is a summary of all eight publications from this review series.

 

Follow
×

Follow

us on our social networks.

Email: hirnec@coh.org