PMID- 23959366
OWN - NLM
STAT- MEDLINE
DCOM- 20140404
LR  - 20220408
IS  - 1759-5037 (Electronic)
IS  - 1759-5029 (Linking)
VI  - 9
IP  - 10
DP  - 2013 Oct
TI  - The role of FOXO1 in beta-cell failure and type 2 diabetes mellitus.
PG  - 615-23
LID - 10.1038/nrendo.2013.157 [doi]
AB  - Over the past two decades, insulin resistance has been considered essential to 
      the aetiology of type 2 diabetes mellitus (T2DM). However, insulin resistance 
      does not lead to T2DM unless it is accompanied by pancreatic beta-cell dysfunction, 
      because healthy beta cells can compensate for insulin resistance by increasing in 
      number and functional output. Furthermore, beta-cell mass is decreased in patients 
      with diabetes mellitus, suggesting a primary role for beta-cell dysfunction in the 
      pathogenesis of T2DM. The dysfunction of beta cells can develop through various 
      mechanisms, including oxidative, endoplasmic reticulum or hypoxic stress, as well 
      as via induction of cytokines; these processes lead to apoptosis, uncontrolled 
      autophagy and failure to proliferate. Transdifferentiation between beta cells and alpha 
      cells occurs under certain pathological conditions, and emerging evidence 
      suggests that beta-cell dedifferentiation or transdifferentiation might account for 
      the reduction in beta-cell mass observed in patients with severe T2DM. FOXO1, a key 
      transcription factor in insulin signalling, is implicated in these mechanisms. 
      This Review discusses advances in our understanding of the contribution of FOXO1 
      signalling to the development of beta-cell failure in T2DM.
FAU - Kitamura, Tadahiro
AU  - Kitamura T
AD  - Metabolic Signal Research Centre, Institute for Molecular and Cellular 
      Regulation, Gunma University, 3-39-15, Showa-machi, Maebashi, Gunma 371-8512, 
      Japan. kitamura@gunma-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20130820
PL  - England
TA  - Nat Rev Endocrinol
JT  - Nature reviews. Endocrinology
JID - 101500078
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Transcription Factors)
SB  - IM
MH  - Diabetes Mellitus, Type 2/*metabolism/*pathology
MH  - Forkhead Box Protein O1
MH  - Forkhead Transcription Factors/genetics/*metabolism
MH  - Humans
MH  - Insulin-Secreting Cells/*metabolism/*pathology
MH  - Oxidative Stress/physiology
EDAT- 2013/08/21 06:00
MHDA- 2014/04/05 06:00
CRDT- 2013/08/21 06:00
PHST- 2013/08/21 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2014/04/05 06:00 [medline]
AID - nrendo.2013.157 [pii]
AID - 10.1038/nrendo.2013.157 [doi]
PST - ppublish
SO  - Nat Rev Endocrinol. 2013 Oct;9(10):615-23. doi: 10.1038/nrendo.2013.157. Epub 
      2013 Aug 20.