Dysfunction of Persisting β Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis

Cell Rep. 2020 Apr 7;31(1):107469. doi: 10.1016/j.celrep.2020.03.033.


Type 2 diabetes is characterized by peripheral insulin resistance and insufficient insulin release from pancreatic islet β cells. However, the role and sequence of β cell dysfunction and mass loss for reduced insulin levels in type 2 diabetes pathogenesis are unclear. Here, we exploit freshly explanted pancreas specimens from metabolically phenotyped surgical patients using an in situ tissue slice technology. This approach allows assessment of β cell volume and function within pancreas samples of metabolically stratified individuals. We show that, in tissue of pre-diabetic, impaired glucose-tolerant subjects, β cell volume is unchanged, but function significantly deteriorates, exhibiting increased basal release and loss of first-phase insulin secretion. In individuals with type 2 diabetes, function within the sustained β cell volume further declines. These results indicate that dysfunction of persisting β cells is a key factor in the early development and progression of type 2 diabetes, representing a major target for diabetes prevention and therapy.

Keywords: Type 2 diabetes; beta cell function; beta cell mass; human pancreas; insulin secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology*
  • Female
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / physiology
  • Insulin Secretion / physiology
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology*
  • Islets of Langerhans / metabolism
  • Male
  • Middle Aged
  • Pancreas / metabolism


  • Blood Glucose
  • Insulin
  • Glucose