Dysfunction of pancreatic beta cells is a key contributor to type 2 diabetes (T2D). Each beta cell stores insulin in several thousand organelles termed insulin secretory granules (SG), which release insulin extracellularly when blood glucose is elevated. So far, our understanding of the principles governing insulin SG turnover remains very rudimental and derives almost exclusively from ex vivo experiments using isolated pancreatic islets. To overcome the existing translational gap to humans, researchers of the German Center for Diabetes Research (DZD) have developed a new in vivo model (a transgenic pig model) that allows studying secretory insulin granule turnover in vivo.
Pancreatic beta cells produce, store and secrete insulin upon elevated blood glucose levels. However, the highly regulated process of insulin secretion, especially its molecular features and the stimuli behind this process have not yet been fully understood. Furthermore, the current understanding of beta cell function is mostly derived from studies of ex vivo isolated islets in rodent models. To overcome this translational gap and to study insulin secretory granule turnover in vivo, a national research team under the lead of scientists from the DZD-partner 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.
The results of this highly collaborative project have been published in the renowned journal `Proceedings of the National Academy of Sciences of the United States of America (PNAS)`, given the likelihood that this novel large animal model close to humans will provide insight into the turnover of insulin pools in physiological and pathological conditions resembling human type 2 diabetes.
Kemter E., Müller, A., … Wolf, E., Solimena, M.: Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs. PNAS (2021)