The islets of Langerhans continue to reveal their secrets

Pancreatic islets, which are critical for glucose homeostasis, are endocrine microorgans embedded in the exocrine pancreas; their location has often limited studying their function. In 2019, advances in islet biology were achieved with new technologies extending findings from several decades ago and with conceptual advances built on findings from other fields.

Key advances

• Somatostatin-producing δ-cells have motile processes or filopodia that extend the reach of their direct contact to capillaries and other hormonal cells within the pancreatic islet².

• Imaging mass cytometry of islets from young adults with recent onset of type 1 diabetes mellitus (T1DM) effectively used this rare tissue to document the progression of T1DM and support the concept of plasticity of the human glucagon-producing α-cells³.

• Imaging mass cytometry of islets from young adults with recent onset of T1DM inferred the progression of T1DM with changes in the β-cell phenotype preceding their destruction with simultaneous recruitment of CD8⁺ and CD4⁺ T cells⁴.

• In NOD mice, senescent β-cells accumulate during prediabetes and further promote the immune destruction; their selective removal by senolytic drugs prevented the onset of T1DM⁸.

• In mouse models (using acute insulin resistance or a high-fat diet), metabolic stress accelerated the senescence of β-cells, which mimics the findings of an increased proportion of senescent β-cells in humans with increased age and in those with type 2 diabetes mellitus⁹; their deletion resulted in improved β-cell identity and function.