PMID- 22983116
OWN - NLM
STAT- MEDLINE
DCOM- 20130111
LR  - 20240202
IS  - 1476-4679 (Electronic)
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 14
IP  - 10
DP  - 2012 Oct
TI  - Wolfram syndrome 1 and adenylyl cyclase 8 interact at the plasma membrane to 
      regulate insulin production and secretion.
PG  - 1105-12
LID - 10.1038/ncb2578 [doi]
AB  - Endoplasmic reticulum (ER) stress causes pancreatic beta-cell dysfunction and 
      contributes to beta-cell loss and the progression of type 2 diabetes. Wolfram 
      syndrome 1 (WFS1) has been shown to be an important regulator of the ER stress 
      signalling pathway; however, its role in beta-cell function remains unclear. Here we 
      provide evidence that WFS1 is essential for glucose- and glucagon-like peptide 1 
      (GLP-1)-stimulated cyclic AMP production and regulation of insulin biosynthesis 
      and secretion. Stimulation with glucose causes WFS1 translocation from the ER to 
      the plasma membrane, where it forms a complex with adenylyl cyclase 8 (AC8), an 
      essential cAMP-generating enzyme in the beta-cell that integrates glucose and GLP-1 
      signalling. ER stress and mutant WFS1 inhibit complex formation and activation of 
      AC8, reducing cAMP synthesis and insulin secretion. These findings reveal that an 
      ER-stress-related protein has a distinct role outside the ER regulating both 
      insulin biosynthesis and secretion. The reduction of WFS1 protein on the plasma 
      membrane during ER stress is a contributing factor for beta-cell dysfunction and 
      progression of type 2 diabetes.
FAU - Fonseca, Sonya G
AU  - Fonseca SG
AD  - Cardiovascular and Metabolism Disease Area, Novartis Institutes for BioMedical 
      Research, Cambridge, Massachusetts 02139, USA. sonya.fonseca@novartis.com
FAU - Urano, Fumihiko
AU  - Urano F
FAU - Weir, Gordon C
AU  - Weir GC
FAU - Gromada, Jesper
AU  - Gromada J
FAU - Burcin, Mark
AU  - Burcin M
LA  - eng
GR  - DK067493/DK/NIDDK NIH HHS/United States
GR  - R37 DK016746/DK/NIDDK NIH HHS/United States
GR  - UL1 RR024992/RR/NCRR NIH HHS/United States
GR  - DK016746/DK/NIDDK NIH HHS/United States
GR  - R01 DK067493/DK/NIDDK NIH HHS/United States
GR  - UL1 TR000448/TR/NCATS NIH HHS/United States
GR  - P60 DK020579/DK/NIDDK NIH HHS/United States
GR  - RR024992/RR/NCRR NIH HHS/United States
GR  - R01 DK016746/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20120916
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Insulin)
RN  - 0 (Membrane Proteins)
RN  - 0 (wolframin protein)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
RN  - EC 4.6.1.1 (adenylyl cyclase 8)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
RIN - Nat Cell Biol. 2015 Jan;17(1):105. PMID: 25679031
MH  - Adenylyl Cyclases/chemistry/*metabolism
MH  - Animals
MH  - Cell Membrane/chemistry/*metabolism
MH  - Cells, Cultured
MH  - Cyclic AMP/biosynthesis
MH  - Endoplasmic Reticulum Stress
MH  - Glucagon-Like Peptide 1/pharmacology
MH  - Glucose/pharmacology
MH  - Humans
MH  - Insulin/*biosynthesis/metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/metabolism
MH  - Male
MH  - Membrane Proteins/chemistry/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mutation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
PMC - PMC3589109
MID - NIHMS445530
EDAT- 2012/09/18 06:00
MHDA- 2013/01/12 06:00
PMCR- 2013/03/05
CRDT- 2012/09/18 06:00
PHST- 2012/04/26 00:00 [received]
PHST- 2012/08/10 00:00 [accepted]
PHST- 2012/09/18 06:00 [entrez]
PHST- 2012/09/18 06:00 [pubmed]
PHST- 2013/01/12 06:00 [medline]
PHST- 2013/03/05 00:00 [pmc-release]
AID - ncb2578 [pii]
AID - 10.1038/ncb2578 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2012 Oct;14(10):1105-12. doi: 10.1038/ncb2578. Epub 2012 Sep 16.