PMID- 28753672
OWN - NLM
STAT- MEDLINE
DCOM- 20171002
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 7
DP  - 2017
TI  - An increase in immature beta-cells lacking Glut2 precedes the expansion of beta-cell 
      mass in the pregnant mouse.
PG  - e0182256
LID - 10.1371/journal.pone.0182256 [doi]
LID - e0182256
AB  - A compensatory increase in beta-cell mass occurs during pregnancy to counter the 
      associated insulin resistance, and a failure in adaptation is thought to 
      contribute to gestational diabetes. Insulin-expressing but 
      glucose-transporter-2-low (Ins+Glut2LO) progenitor cells are present in mouse and 
      human pancreas, being predominantly located in extra-islet beta-cell clusters, and 
      contribute to the regeneration of the endocrine pancreas following induced 
      ablation. We therefore sought to investigate the contribution of Ins+Glut2LO 
      cells to beta-cell mass expansion during pregnancy. Female C57Bl/6 mice were time 
      mated and pancreata were collected at gestational days (GD) 6, 9, 12, 15, and 18, 
      and postpartum D7 (n = 4/time-point) and compared to control (non-pregnant) 
      animals. Beta cell mass, location, proliferation (Ki67+), and proportion of 
      Ins+Glut2LO cells were measured using immunohistochemistry and bright field or 
      confocal microscopy. Beta cell mass tripled by GD18 and beta-cell proliferation 
      peaked at GD12 in islets (>/=6 beta-cells) and small beta-cell clusters (1-5 beta-cells). 
      The proportion and fraction of Ins+Glut2LO cells undergoing proliferation 
      increased significantly at GD9 in both islets and clusters, preceding the 
      increase in beta-cell mass and proliferation, and their proliferation within 
      clusters persisted until GD15. The overall number of clusters increased 
      significantly at GD9. Quantitative PCR showed a significant increase in Pdx1 
      presence at GD9 vs. GD18 or control pancreas, and Pdx1 was visualized by 
      immunohistochemistry within both Ins+Glut2LO and Ins+Glut2HI cells within 
      clusters. These results indicate that Ins+Glut2LO cells are likely to contribute 
      to beta-cell mass expansion during pregnancy.
FAU - Beamish, Christine A
AU  - Beamish CA
AD  - Department of Physiology and Pharmacology, Western University, London, ON, 
      Canada.
AD  - Children's Health Research Institute, London, ON, Canada.
AD  - Lawson Health Research Institute, St Joseph Health Care, London, ON, Canada.
FAU - Zhang, Linhao
AU  - Zhang L
AD  - Lawson Health Research Institute, St Joseph Health Care, London, ON, Canada.
AD  - West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
FAU - Szlapinski, Sandra K
AU  - Szlapinski SK
AD  - Department of Physiology and Pharmacology, Western University, London, ON, 
      Canada.
AD  - Lawson Health Research Institute, St Joseph Health Care, London, ON, Canada.
FAU - Strutt, Brenda J
AU  - Strutt BJ
AD  - Children's Health Research Institute, London, ON, Canada.
FAU - Hill, David J
AU  - Hill DJ
AUID- ORCID: 0000-0002-2490-5678
AD  - Department of Physiology and Pharmacology, Western University, London, ON, 
      Canada.
AD  - Children's Health Research Institute, London, ON, Canada.
AD  - Lawson Health Research Institute, St Joseph Health Care, London, ON, Canada.
AD  - Department of Medicine, Western University, London, ON, Canada.
LA  - eng
PT  - Journal Article
DEP - 20170728
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Glucose Transporter Type 2)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/genetics/physiology
MH  - Diabetes, Gestational/*metabolism
MH  - Female
MH  - Gestational Age
MH  - Glucose Transporter Type 2/deficiency/*metabolism
MH  - Insulin-Secreting Cells/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polymerase Chain Reaction
MH  - Pregnancy
PMC - PMC5533342
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/07/29 06:00
MHDA- 2017/10/03 06:00
PMCR- 2017/07/28
CRDT- 2017/07/29 06:00
PHST- 2016/11/06 00:00 [received]
PHST- 2017/07/14 00:00 [accepted]
PHST- 2017/07/29 06:00 [entrez]
PHST- 2017/07/29 06:00 [pubmed]
PHST- 2017/10/03 06:00 [medline]
PHST- 2017/07/28 00:00 [pmc-release]
AID - PONE-D-16-44029 [pii]
AID - 10.1371/journal.pone.0182256 [doi]
PST - epublish
SO  - PLoS One. 2017 Jul 28;12(7):e0182256. doi: 10.1371/journal.pone.0182256. 
      eCollection 2017.