Diabetes research: A new model for studies of beta-cell function

The beta cells of the pancreas synthesize, store and secrete the hormone insulin, which controls the level of glucose in the blood. Perturbation of the function of these cells is a major cause of adult-onset Type-2 diabetes, a condition that affects several million people around the world. Each beta cell contains thousands of organelles, known as secretory granules (SG), which release insulin into the bloodstream when the level of blood sugar rises. However, only a small fraction of the granules in each cell is released – which preferentially consists of those that were most recently synthesized. The mechanisms responsible for this process are not fully understood. In addition, our current knowledge of beta-cell function is largely based on studies on ex-vivo cell clusters (islets) isolated from rodents. In order to close the translational gap between these model systems and humans, CiMM scientists, together with researchers based at the Paul Langerhans Institute of the Helmholtz Zentrum München at the University Hospital Carl Gustav Carus and Faculty of Medicine of TU Dresden (PLID), have developed a transgenic pig model, which makes it possible for the first time to reproduce the pattern of insulin turnover seen in humans when levels of blood sugar are within the normal range. The authors of the study are convinced that the successful generation and characterization of the new experimental model represent an important step on the way to overcoming the limitations that currently hamper beta-cell research. SOFIA pigs can now be crossed with other pig strains that serve as model systems for the study of diabetes mellitus, in order to determine the rates of synthesis and turnover of insulin secretory granules under pathological conditions.
Original publication:
Kemter E, Müller A, Neukam M, Ivanova A, Klymiuk N, Renner S, Yang K, Broichhagen J, Kurome M, Zakhartchenko V, Kessler B, Knoch KP, Bickle M, Ludwig B, Johnsson K, Lickert H, Kurth T, Wolf E, Solimena M. Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs. Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):e2107665118. doi: 10.1073/pnas.2107665118.

doi: 10.1073/pnas.2107665118