Illuminating the complete ß-cell mass of the human pancreas- signifying a new view on the islets of Langerhans

Abstract

Pancreatic islets of Langerhans play a pivotal role in regulating blood glucose homeostasis, but critical information regarding their mass, distribution and composition is lacking within a whole organ context. Here, we apply a 3D imaging pipeline to generate a complete account of the insulin-producing islets throughout the human pancreas at a microscopic resolution and within a maintained spatial 3D context. These data show that human islets are far more heterogenous than previously accounted for with regards to their size distribution and cellular make up. By deep tissue 3D imaging, this in-depth study demonstrates that 50% of the human insulin-expressing islets are virtually devoid of glucagon-producing α-cells, an observation with significant implications for both experimental and clinical research.

Machine-learning-guided recognition of α and β cells from label-free infrared micrographs of living human islets of Langerhans

“…Neglecting cells from the most abundant class (i.e. β cells) could lead to a biased model due to the high biological heterogeneity of Langerhans islets (Table S2 ) 24 , considering that several algorithms are built on the hypothesis of balanced classes as inputs). To address this, we employed the Synthetic Minority Oversampling Technique (SMOTE) 25 .…”

Impaired islet function and normal exocrine enzyme secretion occur with low inter-regional variation in type 1 diabetes

“…A recent 3D whole-pancreas imaging study reported uniform distribution of insulin volumes across pancreas regions. 38 Nevertheless, such studies are scarce, highlighting the need to improve our understanding of whole-pancreas islet distribution in 2D versus 3D.…”