PMID- 25695910
OWN - NLM
STAT- MEDLINE
DCOM- 20160328
LR  - 20181113
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 29
IP  - 5
DP  - 2015 May
TI  - Activation of Melatonin Signaling Promotes beta-Cell Survival and Function.
PG  - 682-92
LID - 10.1210/me.2014-1293 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is characterized by pancreatic islet failure due 
      to loss of beta-cell secretory function and mass. Studies have identified a link 
      between a variance in the gene encoding melatonin (MT) receptor 2, T2DM, and 
      impaired insulin secretion. This genetic linkage raises the question whether MT 
      signaling plays a role in regulation of beta-cell function and survival in T2DM. To 
      address this postulate, we used INS 832/13 cells to test whether activation of MT 
      signaling attenuates proteotoxicity-induced beta-cell apoptosis and through which 
      molecular mechanism. We also used nondiabetic and T2DM human islets to test the 
      potential of MT signaling to attenuate deleterious effects of glucotoxicity and 
      T2DM on beta-cell function. MT signaling in beta-cells (with duration designed to mimic 
      typical nightly exposure) significantly enhanced activation of the cAMP-dependent 
      signal transduction pathway and attenuated proteotoxicity-induced beta-cell 
      apoptosis evidenced by reduced caspase-3 cleavage ( approximately 40%), decreased activation of 
      stress-activated protein kinase/Jun-amino-terminal kinase ( approximately 50%) and diminished 
      oxidative stress response. Activation of MT signaling in human islets was shown 
      to restore glucose-stimulated insulin secretion in islets exposed to chronic 
      hyperglycemia as well as in T2DM islets. Our data suggest that beta-cell MT 
      signaling is important for the regulation of beta-cell survival and function and 
      implies a preventative and therapeutic potential for preservation of beta-cell mass 
      and function in T2DM.
FAU - Costes, Safia
AU  - Costes S
AD  - Department of Medicine (S.C., M.B., A.P.T., A.V.M.), David Geffen School of 
      Medicine, University of California Los Angeles, Los Angeles, California 90095; 
      and Department of Physiology and Biomedical Engineering (A.V.M.), Mayo Clinic 
      School of Medicine, Mayo Clinic Rochester, Minnesota 55905.
FAU - Boss, Marti
AU  - Boss M
FAU - Thomas, Anthony P
AU  - Thomas AP
FAU - Matveyenko, Aleksey V
AU  - Matveyenko AV
LA  - eng
GR  - R01 DK098468/DK/NIDDK NIH HHS/United States
GR  - R01DK098468/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150219
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Receptors, Melatonin)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - Diabetes Mellitus, Type 2/metabolism
MH  - Humans
MH  - Insulin-Secreting Cells/*physiology
MH  - Melatonin/*physiology
MH  - Rats
MH  - Receptors, Melatonin/metabolism
MH  - Signal Transduction
PMC - PMC4415205
EDAT- 2015/02/20 06:00
MHDA- 2016/03/29 06:00
PMCR- 2016/05/01
CRDT- 2015/02/20 06:00
PHST- 2015/02/20 06:00 [entrez]
PHST- 2015/02/20 06:00 [pubmed]
PHST- 2016/03/29 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - ME-14-1293 [pii]
AID - 10.1210/me.2014-1293 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2015 May;29(5):682-92. doi: 10.1210/me.2014-1293. Epub 2015 Feb 
      19.