TY - JOUR TI - Sequential in vivo labeling of insulin secretory granule pools in INS - SNAP transgenic pigs AU - Kemter, Elisabeth AU - Müller, Andreas AU - Neukam, Martin AU - Ivanova, Anna AU - Klymiuk, Nikolai AU - Renner, Simone AU - Yang, Kaiyuan AU - Broichhagen, Johannes AU - Kurome, Mayuko AU - Zakhartchenko, Valeri AU - Kessler, Barbara AU - Knoch, Klaus-Peter AU - Bickle, Marc AU - Ludwig, Barbara AU - Johnsson, Kai AU - Lickert, Heiko AU - Kurth, Thomas AU - Wolf, Eckhard AU - Solimena, Michele T2 - Proceedings of the National Academy of Sciences AB - β cells produce, store, and secrete insulin upon elevated blood glucose levels. Insulin secretion is a highly regulated process. The probability for insulin secretory granules to undergo fusion with the plasma membrane or being degraded is correlated with their age. However, the molecular features and stimuli connected to this behavior have not yet been fully understood. Furthermore, our understanding of β cell function is mostly derived from studies of ex vivo isolated islets in rodent models. To overcome this translational gap and study insulin secretory granule turnover in vivo, we have generated a transgenic pig model with the SNAP-tag fused to insulin. We demonstrate the correct targeting and processing of the tagged insulin and normal glycemic control of the pig model. Furthermore, we show specific single- and dual-color granular labeling of in vivo–labeled pig pancreas. This model may provide unprecedented insights into the in vivo insulin secretory granule behavior in an animal close to humans. DA - 2021/09/14/ PY - 2021 DO - 10.1073/pnas.2107665118 DP - DOI.org (Crossref) VL - 118 IS - 37 SP - e2107665118 J2 - Proc Natl Acad Sci USA LA - en SN - 0027-8424, 1091-6490 UR - http://www.pnas.org/lookup/doi/10.1073/pnas.2107665118 Y2 - 2021/10/26/12:27:21 KW - WP5 ER -