title: Role of pancreatic β-cell death and inflammation in diabetes.
abstract: Apoptosis of pancreatic β-cells is the final step in the development of type 1 diabetes (T1D), leading to critically diminished β-cell mass and contributing to the onset of hyperglycaemia. The spontaneous apoptosis of pancreatic β-cells during pancreas ontogeny also induces cell death-associated inflammation, stimulates antigen-presenting cells and sensitizes naïve diabetogenic T cells. The role of pancreatic β-cell death in type 2 diabetes (T2D) is less clear. In the preclinical period of T2D, hyperinsulinaemia and β-cell hyperplasia develop to compensate for insulin resistance, which is clearly seen in animal models of T2D. For the development of overt T2D, relative insulin deficiency is critical in addition to insulin resistance. Insulin deficiency could be due to β-cell dysfunction and/or decreased β-cell mass. Pancreatic β-cell apoptosis due to lipid injury (lipoapoptosis), endoplasmic reticulum (ER) stress or JNK activation could contribute to the decreased β-cell mass in T2D. Activation of inflammasomes by lipid injury, ER stress, human islet amyloid polypeptide, hyperglycaemia or autophagy insufficiency could also lead to β-cell death or dysfunction. Thus, β-cell death and cell death-associated inflammation through innate immune receptors could be important in both T1D and T2D.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: W
authors.initials: W
authors.lastname: Quan
authors.forename: E-K
authors.initials: EK
authors.lastname: Jo
authors.forename: M-S
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D016923:Cell Death; D003920:Diabetes Mellitus / Q000209:etiology* / Q000473:pathology; D006801:Humans; D058847:Inflammasomes / Q000502:physiology; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000473:pathology* / Q000502:physiology*
chemical_list: D058847:Inflammasomes
keywords: autophagy; cell death; inflammasomes; inflammation; β-cells