In rodents, the endocrine pancreas consists of islets of Langerhans scattered throughout the exocrine acinar tissue and accounts for a minor fraction of the organ’s total volume. This anatomical configuration, combined with the small size of the islets and the fact that they are embedded within enzyme-rich exocrine tissue, has historically made isolating intact and functional islets a considerable challenge, particularly for metabolic studies that require pure islet tissue.

Early efforts in the 1960s used free-hand microdissection to isolate small numbers of islets from rodent pancreas tissue and primarily targeted hypertrophic islets in obese rodents, in which surface islets are fairly accessible. Another method involved inducing pancreatic atrophy by ligating one of the main pancreatic ducts to facilitate islet dissection. However, these techniques were associated with notable pathological conditions, such as spontaneous hyperglycaemia in animals with hypertrophic islets and fibrosis or atrophy of the pancreas following duct ligation. Although these techniques provided foundational insights, their limited scalability and the pathological states associated with them highlighted the need for more advanced methods to reliably isolate intact islets.