β-Cell Deficit and Increased β-Cell Apoptosis in Humans With Type 2 Diabetes

By A. Butler, J. Janson, S. Bonner-Weir, R. Ritzel, Robert A. Rizza, P. Butler. Diabetes, 2003

3,736 citations recorded by the source corpus.

Type 2 diabetes is characterized by impaired insulin secretion. Some but not all studies suggest that a decrease in β-cell mass contributes to this. We examined pancreatic tissue from 124 autopsies: 91 obese cases (BMI >27 kg/m2; 41 with type 2 diabetes, 15 with impaired fasting glucose [IFG], and 35 nondiabetic subjects) and 33 lean cases (BMI <25 kg/m2; 16 type 2 diabetic and 17 nondiabetic subjects). We measured relative β-cell volume, frequency of β-cell apoptosis and replication, and new islet formation from exocrine ducts (neogenesis). Relative β-cell volume was increased in obese versus lean nondiabetic cases (P = 0.05) through the mechanism of increased neogenesis (P < 0.05). Obese humans with IFG and type 2 diabetes had a 40% (P < 0.05) and 63% (P < 0.01) deficit and lean cases of type 2 diabetes had a 41% deficit (P < 0.05) in relative β-cell volume compared with nondiabetic obese and lean cases, respectively. The frequency of β-cell replication was very low in all cases and no different among groups. Neogenesis, while increased with obesity, was comparable in obese type 2 diabetic, IFG, or nondiabetic subjects and in lean type 2 diabetic or nondiabetic subjects. However, the frequency of β-cell apoptosis was increased 10-fold in lean and 3-fold in obese cases of type 2 diabetes compared with their respective nondiabetic control group (P < 0.05). We conclude that β-cell mass is decreased in type 2 diabetes and that the mechanism underlying this is increased β-cell apoptosis. Since the major defect leading to a decrease in β-cell mass in type 2 diabetes is increased apoptosis, while new islet formation and β-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 diabetes, because this approach might actually reverse the disease to a degree rather than just palliate glycemia.

Subfields: Genetics, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/80732c95d19c3151dc35ace138967547bc1378a6

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In Molecular Biology

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In Surgery

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Citations in the corpus

• Thioredoxin-interacting protein mediates ER stress-induced β cell death through initiation of the inflammasome (2012, background): “In contrast, type 2 diabetes is a state of relative insulin deficiency as a result of b cell dysfunction and death caused by a combination of increased circulating glucose and saturated fatty acids and development of inflammation (Butler et al., 2003; Donath and Halban, 2004).”
• Pathogenesis of type 2 diabetes mellitus. (2004, background): “On routine histologic examination, the islets of Langerhans appear normal with the exception of beta-cell degranulation [87–90].”
• Initiation and execution of lipotoxic ER stress in pancreatic β-cells (2008, background): “Intervention strategies in the former pathways should be developed to prevent lipotoxic βcell loss, whereas promotion of ATF6 signaling might boost β-cell defense mechanisms in T2D.”