An international team of researchers led by PLID scientists used optogenetic systems to investigate in the zebrafish model how the Ca2+ response is orchestrated spatially and temporally and what role individual beta cells play in the response to a glucose stimulus. The study provides crucial insights into the functional hierarchy of pancreatic beta cells in the response to glucose and also highlights the role of vitamin B6 in this process. It also provides a new understanding of how beta cells coordinate insulin secretion to regulate blood glucose levels.

Researchers at the PLID have presented a novel protocol that is set to transform the analysis of three-dimensional electron microscopy datasets. They have developed a detailed guide aimed at researchers in biology and medicine, providing a modular and user-friendly workflow to unravel the intricate details of cellular ultrastructure.

A group of PLID scientists has teamed up with international experts in the field to review the scientific evidence for the existence of a close interdependence between various viral infections and metabolic diseases. The review has now been published in the renowned journal Lancet Diabetes Endocrinology.

Gastrointestinal hormones are important and established regulators of energy and glucose homeostasis. However, despite the known or increasing role of these hormones in metabolism, it is still controversial whether impairments in their fasting or postprandial profiles are observed in metabolic diseases and whether they contribute to the progression of hyperglycemia toward the development of type 2 diabetes. This question has now been addressed by researchers from the Paul Langerhans Institute Dresden, together with scientists from Tübingen, Boston, London and Zurich.

Detailed characterization of human pancreatic islets is key to elucidate the pathophysiology of all forms of diabetes mellitus, including its most common form known as type 2 diabetes. However, access to pancreatic islets is limited and pancreatic tissue for islet retrieval can be either obtained from cadaveric or brain-dead organ donors or from patients undergoing pancreatectomy, henceforth defined as living donors.

Zebrafish can recover from diabetes by regenerating insulin-secreting beta cells in the pancreas. However, the cellular dynamics underlying this ability have remained unexplored. To fill this knowledge gap, scientists at the Paul Langerhans Institute Dresden used single-cell transcriptomics to track de novo beta cell regeneration during the development and regeneration of diabetes in zebrafish.

A national research team under the lead of scientists from the Paul Langerhans Institute of the Helmholtz Zentrum München at the University Hospital Carl Gustav Carus and Faculty of Medicine of TU Dresden (PLID) and the LMU Munich has generated a transgenic pig model allowing for the first time the in vivo fluorescent labeling of age-distinct insulin secretory granule pools, hence providing a close-to-life readout of insulin turnover in normoglycemic conditions.

Microtubules are a part of cytoskeleton and act as highways for the transport of vesicles within the cell. Now, an international team led by scientists of the PLID, together with the CSBD, MPI-CBG, Janelia Research Campus, CMCB, Fondazione Human Technopole as well as the EPFL used high resolution 3D electron microscopy to image insulin secreting pancreatic islet beta cells in their entirety at an unprecedented resolution and reconstructed all insulin secretory granules, microtubules, mitochondria, Golgi apparati, and centrioles to generate a comprehensive spatial map of microtubule-organelle interactions.

The discovery of insulin in 1921 has been one of greatest scientific achievements of the 20th century. Since then, the availability of insulin has shifted the focus of diabetes treatment from trying to keep patients alive to saving and improving the life of millions. Now, scientists of the PLID published a new review article on the making of insulin in a special issue of “Diabetologia”. It sheds light on the most recent findings on insulin synthesis and highlights their relevance in diabetes.

In type 1 diabetes (T1D), autoimmune destruction of pancreatic beta cells leads to insulin deficiency and loss of glycemic control. However, knowledge about pathophysiology in T1D remains incomplete, also due to a lack of technologies to study the live human pancreas in T1D.

Type-2 diabetes (T2D) is characterized by peripheral insulin resistance and insufficient insulin release from pancreatic islet beta cells. However, it is still unclear if the inadequate insulin levels during T2D development are the result of beta cell dysfunction and/or loss of beta cell numbers.

One goal of modern diabetes research is to improve the effect of therapeutic insulin on the body. In a new study, the researchers have now solved a critical part of the puzzle by showing how insulin interacts with its receptor at a second binding site.

Researchers from La Trobe University in Australia and the PLID have identified that the protein Atp6ap2 is essential for the correct functioning of pancreatic beta cells. When this protein was switched off in the beta cells of mice their blood glucose levels dramatically increased.

Contemporary research of beta cell biology in context of type-2 diabetes is based mainly on the long-standing technique for isolation of the pancreatic islets of Langerhans. Scientists of the PLID developed a new approach to isolate islets from snap frozen surgical specimens donated by metabolically phenotyped pancreatectomized patients. A new review article published in “Molecular Metabolism” explains how this platform may represent a paradigmatic shift for the study of human islets and diabetes research.

Researchers from PLID together with colleagues from Imperial College London and other research institutes from the UK, Canada and Italy have observed amazing cell interactions: The beta cells of the pancreas work as highly-connected clusters, known as islets, and their responses to rising blood glucose levels are coordinated by small teams of “leader cells”. To show that, the research teams developed an innovative imaging technique which allowed them to observe beta cells’ hierarchical relationship in live animals including in zebrafish and mouse.

In Germany, about one in ten people suffer from diabetes and diabetes patients still die two to three times more frequently from cardiovascular diseases such as heart attacks and strokes. Newly developed drugs for diabetes therapy are therefore expected to reduce the number of cardiovascular deaths. Scientists from the PLID have, together with international colleagues, investigated for the first time whether semaglutide in tablet form leads to a reduction in cardiovascular events. An international, randomized double-blind study with 3,183 participants was therefore conducted in 21 countries in parallel.

With the participation of researchers from the PLID, a GLP-1 receptor agonist in the form of tablets could for the first time be compared with the most common second-line therapy of T2D, a DPP-IV inhibitor. The results of the PIONEER-3 trial have now been published in the renowned journal ´Journal of the American Medical Association (JAMA)´.

Scientists from PLID, University Hospital Carl Gustav Carus and Lipotype GmbH joined their forces and developed a new shotgun lipidomics method for the molecular profiling of brown and white adipose tissue.

Inflammatory processes are a natural defense reaction of the immune system against pathogens. If they get out of control, they can however lead to diseases themselves. The protein DEL-1, is a central actor that ensures that excessive inflammation subsides. Scientists from the Medical Faculty Carl Gustav Carus of the TU Dresden and the National Center for Tumor Diseases Dresden (NCT/UCC), together with an international team of researchers, were able to demonstrate the importance and basic function of this protein.

Scientists at PLID have found out how cells react to insulin. It was previously known that insulin transmits a signal through receptors on the cell surface, however the Coskun group was now able to observe a change in the shape of the receptors.

A collaborative study has identified a novel cluster of dysregulated genes in the pancreatic islets of patients with type 2 diabetes. The study is part of the EU-Innovative Medicine Initiative (IMI) research consortium IMIDIA.