TY - JOUR
T1 - Natural history of β-cell adaptation and failure in type 2 diabetes
AU - Alejandro, Emilyn U.
AU - Gregg, Brigid
AU - Blandino-Rosano, Manuel
AU - Cras-Méneur, Corentin
AU - Bernal-Mizrachi, Ernesto
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Type 2 diabetes mellitus (T2D) is a complex disease characterized by β-cell failure in the setting of insulin resistance. The current evidence suggests that genetic predisposition, and environmental factors can impair the capacity of the β-cells to respond to insulin resistance and ultimately lead to their failure. However, genetic studies have demonstrated that known variants account for less than 10% of the overall estimated T2D risk, suggesting that additional unidentified factors contribute to susceptibility of this disease. In this review, we will discuss the different stages that contribute to the development of β-cell failure in T2D. We divide the natural history of this process in three major stages: susceptibility, β-cell adaptation and β-cell failure, and provide an overview of the molecular mechanisms involved. Further research into mechanisms will reveal key modulators of β-cell failure and thus identify possible novel therapeutic targets and potential interventions to protect against β-cell failure.
AB - Type 2 diabetes mellitus (T2D) is a complex disease characterized by β-cell failure in the setting of insulin resistance. The current evidence suggests that genetic predisposition, and environmental factors can impair the capacity of the β-cells to respond to insulin resistance and ultimately lead to their failure. However, genetic studies have demonstrated that known variants account for less than 10% of the overall estimated T2D risk, suggesting that additional unidentified factors contribute to susceptibility of this disease. In this review, we will discuss the different stages that contribute to the development of β-cell failure in T2D. We divide the natural history of this process in three major stages: susceptibility, β-cell adaptation and β-cell failure, and provide an overview of the molecular mechanisms involved. Further research into mechanisms will reveal key modulators of β-cell failure and thus identify possible novel therapeutic targets and potential interventions to protect against β-cell failure.
KW - Glucolipotoxicity
KW - Insulin resistance
KW - Islet biology
KW - β-cell development
KW - β-cell failure
KW - β-cell programming
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U2 - 10.1016/j.mam.2014.12.002
DO - 10.1016/j.mam.2014.12.002
M3 - Review article
C2 - 25542976
AN - SCOPUS:84937071614
VL - 42
SP - 19
EP - 41
JO - Molecular Aspects of Medicine
JF - Molecular Aspects of Medicine
SN - 0098-2997
ER -