PMID- 25101872
OWN - NLM
STAT- MEDLINE
DCOM- 20151106
LR  - 20211021
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Print)
IS  - 1553-7390 (Linking)
VI  - 10
IP  - 8
DP  - 2014 Aug
TI  - A genetic strategy to measure circulating Drosophila insulin reveals genes 
      regulating insulin production and secretion.
PG  - e1004555
LID - 10.1371/journal.pgen.1004555 [doi]
LID - e1004555
AB  - Insulin is a major regulator of metabolism in metazoans, including the fruit fly 
      Drosophila melanogaster. Genome-wide association studies (GWAS) suggest a genetic 
      basis for reductions of both insulin sensitivity and insulin secretion, 
      phenotypes commonly observed in humans with type 2 diabetes mellitus (T2DM). To 
      identify molecular functions of genes linked to T2DM risk, we developed a genetic 
      tool to measure insulin-like peptide 2 (Ilp2) levels in Drosophila, a model 
      organism with superb experimental genetics. Our system permitted sensitive 
      quantification of circulating Ilp2, including measures of Ilp2 dynamics during 
      fasting and re-feeding, and demonstration of adaptive Ilp2 secretion in response 
      to insulin receptor haploinsufficiency. Tissue specific dissection of this 
      reduced insulin signaling phenotype revealed a critical role for insulin 
      signaling in specific peripheral tissues. Knockdown of the Drosophila orthologues 
      of human T2DM risk genes, including GLIS3 and BCL11A, revealed roles of these 
      Drosophila genes in Ilp2 production or secretion. Discovery of Drosophila 
      mechanisms and regulators controlling in vivo insulin dynamics should accelerate 
      functional dissection of diabetes genetics.
FAU - Park, Sangbin
AU  - Park S
AD  - Department of Developmental Biology, Stanford University School of Medicine, 
      Stanford, California, United States of America.
FAU - Alfa, Ronald W
AU  - Alfa RW
AD  - Department of Developmental Biology, Stanford University School of Medicine, 
      Stanford, California, United States of America; Neuroscience Program, Stanford 
      University School of Medicine, Stanford, California, United States of America.
FAU - Topper, Sydni M
AU  - Topper SM
AD  - Department of Developmental Biology, Stanford University School of Medicine, 
      Stanford, California, United States of America.
FAU - Kim, Grace E S
AU  - Kim GE
AD  - Department of Developmental Biology, Stanford University School of Medicine, 
      Stanford, California, United States of America.
FAU - Kockel, Lutz
AU  - Kockel L
AD  - Department of Developmental Biology, Stanford University School of Medicine, 
      Stanford, California, United States of America.
FAU - Kim, Seung K
AU  - Kim SK
AD  - Department of Developmental Biology, Stanford University School of Medicine, 
      Stanford, California, United States of America; Department of Medicine (Oncology 
      Division) Stanford University School of Medicine, Stanford, California, United 
      States of America; Howard Hughes Medical Institute, Stanford University School of 
      Medicine, Stanford, California, United States of America.
LA  - eng
GR  - T32 MH020016/MH/NIMH NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140807
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (BCL11A protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (GLIS3 protein, human)
RN  - 0 (ILP2 protein, Drosophila)
RN  - 0 (Insulin)
RN  - 0 (Neuropeptides)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/genetics
MH  - DNA-Binding Proteins
MH  - Diabetes Mellitus, Type 2/*genetics/metabolism/pathology
MH  - Drosophila Proteins/*genetics/metabolism
MH  - Drosophila melanogaster/*genetics/metabolism
MH  - Fasting
MH  - Gene Knockdown Techniques
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Insulin/biosynthesis/genetics/*metabolism
MH  - Insulin Resistance/genetics
MH  - Insulin Secretion
MH  - Neuropeptides
MH  - Nuclear Proteins/genetics
MH  - Repressor Proteins
MH  - Signal Transduction/genetics
MH  - Trans-Activators
MH  - Transcription Factors/genetics
PMC - PMC4125106
COIS- The authors have declared that no competing interests exist.
EDAT- 2014/08/08 06:00
MHDA- 2015/11/07 06:00
PMCR- 2014/08/07
CRDT- 2014/08/08 06:00
PHST- 2014/04/16 00:00 [received]
PHST- 2014/06/20 00:00 [accepted]
PHST- 2014/08/08 06:00 [entrez]
PHST- 2014/08/08 06:00 [pubmed]
PHST- 2015/11/07 06:00 [medline]
PHST- 2014/08/07 00:00 [pmc-release]
AID - PGENETICS-D-14-01047 [pii]
AID - 10.1371/journal.pgen.1004555 [doi]
PST - epublish
SO  - PLoS Genet. 2014 Aug 7;10(8):e1004555. doi: 10.1371/journal.pgen.1004555. 
      eCollection 2014 Aug.