TY - JOUR
T1 - A 3D atlas of the dynamic and regional variation of pancreatic innervation in diabetes
AU - Alvarsson, Alexandra
AU - Jimenez-Gonzalez, Maria
AU - Li, Rosemary
AU - Rosselot, Carolina
AU - Tzavaras, Nikolaos
AU - Wu, Zhuhao
AU - Stewart, Andrew F.
AU - Garcia-Ocaña, Adolfo
AU - Stanley, Sarah A.
N1 - Publisher Copyright:
© 2020 The Authors.
PY - 2020/10/7
Y1 - 2020/10/7
N2 - Understanding the detailed anatomy of the endocrine pancreas, its innervation, and the remodeling that occurs in diabetes can provide new insights into metabolic disease. Using tissue clearing and whole-organ imaging, we identified the 3D associations between islets and innervation. This technique provided detailed quantification of α and β cell volumes and pancreatic nerve fibers, their distribution and heterogeneity in healthy tissue, canonical mouse models of diabetes, and samples from normal and diabetic human pancreata. Innervation was highly enriched in the mouse endocrine pancreas, with regional differences. Islet nerve density was increased in nonobese diabetic mice, in mice treated with streptozotocin, and in pancreata of human donors with type 2 diabetes. Nerve contacts with β cells were preserved in diabetic mice and humans. In summary, our whole-organ assessment allows comprehensive examination of islet characteristics and their innervation and reveals dynamic regulation of islet innervation in diabetes.
AB - Understanding the detailed anatomy of the endocrine pancreas, its innervation, and the remodeling that occurs in diabetes can provide new insights into metabolic disease. Using tissue clearing and whole-organ imaging, we identified the 3D associations between islets and innervation. This technique provided detailed quantification of α and β cell volumes and pancreatic nerve fibers, their distribution and heterogeneity in healthy tissue, canonical mouse models of diabetes, and samples from normal and diabetic human pancreata. Innervation was highly enriched in the mouse endocrine pancreas, with regional differences. Islet nerve density was increased in nonobese diabetic mice, in mice treated with streptozotocin, and in pancreata of human donors with type 2 diabetes. Nerve contacts with β cells were preserved in diabetic mice and humans. In summary, our whole-organ assessment allows comprehensive examination of islet characteristics and their innervation and reveals dynamic regulation of islet innervation in diabetes.
UR - http://www.scopus.com/inward/record.url?scp=85092752477&partnerID=8YFLogxK
U2 - 10.1126/sciadv.aaz9124
DO - 10.1126/sciadv.aaz9124
M3 - Article
C2 - 33036983
AN - SCOPUS:85092752477
SN - 2375-2548
VL - 6
JO - Science advances
JF - Science advances
IS - 41
M1 - eaaz9124
ER -