Organisation of the human pancreas in health and in diabetes

Abstract

For much of the last century, our knowledge regarding the pancreas in type 1 and type 2 diabetes was largely derived from autopsy studies of individuals with these disorders or investigations utilising rodent models of either disease. While many important insights emanated from these efforts, the mode for investigation has increasingly seen change due to the availability of transplant-quality organ-donor tissues, improvements in pancreatic imaging, advances in metabolic assessments of living patients, genetic analyses, technological advances for laboratory investigation and more. As a result, many long-standing notions regarding the role for and the changes that occur in the pancreas in individuals with these disorders have come under question, while, at the same time, new issues (e.g., beta cell persistence, disease heterogeneity, exocrine contributions) have arisen. In this article, we will consider the vital role of the pancreas in human health and physiology, including discussion of its anatomical features and dual (exocrine and endocrine) functions. Specifically, we convey changes that occur in the pancreas of those with either type 1 or type 2 diabetes, with careful attention to the facets that may contribute to the pathogenesis of either disorder. Finally, we discuss the emerging unknowns with the belief that understanding the role of the pancreas in type 1 and type 2 diabetes will lead to improvements in disease diagnosis, understanding of disease heterogeneity and optimisation of treatments at a personalised level. Graphical abstract.

Keywords: Anatomy; Endocrine; Exocrine; Function; Pancreas; Review; Type 1 diabetes; Type 2 diabetes.

Fig. 1

Key anatomical features of the human pancreas. (a) Diagram of the pancreas, and surrounding organs. (b) Schematic representation of organisation of the endocrine and exocrine pancreas at the cellular level. (c) Human pancreatic islet showing the four endocrine cell types. Scale bar, 100 μm. This figure is available as part of a downloadable slideset

Fig. 2

Representative images of islets of Langerhans in pancreases from individuals without diabetes and those with type 1 and type 2 diabetes. Pancreatic tissue was stained with H&E or for beta cells (insulin; INS), alpha cells (glucagon; GCG) and T cells (CD3). (a) A pancreatic islet from a healthy donor, showing normal distribution of beta and alpha cells. (b) Insulitic islet with CD3 infiltration (red arrow) in the pancreas of an individual with type 1 diabetes. (c) Islet with amyloid deposits (green arrows), demonstrated by H&E Congo Red staining in the pancreas of an individual with type 2 diabetes. INS, GCG and CD3 staining in the islet from the type 2 diabetic donor is also shown. Scale bars: 100 μm in (a) and (c); 200 μm in (b). This figure is available as part of a downloadable slideset