Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure

Nat Rev Endocrinol. 2020 Jul;16(7):349-362. doi: 10.1038/s41574-020-0355-7. Epub 2020 May 12.


Loss of functional β-cell mass is the key mechanism leading to the two main forms of diabetes mellitus - type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Understanding the mechanisms behind β-cell failure is critical to prevent or revert disease. Basic pathogenic differences exist in the two forms of diabetes mellitus; T1DM is immune mediated and T2DM is mediated by metabolic mechanisms. These mechanisms differentially affect early β-cell dysfunction and eventual fate. Over the past decade, major advances have been made in the field, mostly delivered by studies on β-cells in human disease. These advances include studies of islet morphology and human β-cell gene expression in T1DM and T2DM, the identification and characterization of the role of T1DM and T2DM candidate genes at the β-cell level and the endoplasmic reticulum stress signalling that contributes to β-cell failure in T1DM (mostly IRE1 driven) and T2DM (mostly PERK-eIF2α dependent). Here, we review these new findings, focusing on studies performed on human β-cells or on samples obtained from patients with diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Exocrine Pancreatic Insufficiency / etiology*
  • Exocrine Pancreatic Insufficiency / physiopathology
  • Humans
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / physiology*
  • Signal Transduction / physiology