PMID- 28808079
OWN - NLM
STAT- MEDLINE
DCOM- 20170925
LR  - 20181113
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 235
IP  - 2
DP  - 2017 Nov
TI  - The impact of IUGR on pancreatic islet development and beta-cell function.
PG  - R63-R76
LID - 10.1530/JOE-17-0076 [doi]
AB  - Placental insufficiency is a primary cause of intrauterine growth restriction 
      (IUGR). IUGR increases the risk of developing type 2 diabetes mellitus (T2DM) 
      throughout life, which indicates that insults from placental insufficiency impair 
      beta-cell development during the perinatal period because beta-cells have a central 
      role in the regulation of glucose tolerance. The severely IUGR fetal pancreas is 
      characterized by smaller islets, less beta-cells, and lower insulin secretion. 
      Because of the important associations among impaired islet growth, beta-cell 
      dysfunction, impaired fetal growth, and the propensity for T2DM, significant 
      progress has been made in understanding the pathophysiology of IUGR and 
      programing events in the fetal endocrine pancreas. Animal models of IUGR 
      replicate many of the observations in severe cases of human IUGR and allow us to 
      refine our understanding of the pathophysiology of developmental and functional 
      defects in islet from IUGR fetuses. Almost all models demonstrate a phenotype of 
      progressive loss of beta-cell mass and impaired beta-cell function. This review will 
      first provide evidence of impaired human islet development and beta-cell function 
      associated with IUGR and the impact on glucose homeostasis including the 
      development of glucose intolerance and diabetes in adulthood. We then discuss 
      evidence for the mechanisms regulating beta-cell mass and insulin secretion in the 
      IUGR fetus, including the role of hypoxia, catecholamines, nutrients, growth 
      factors, and pancreatic vascularity. We focus on recent evidence from 
      experimental interventions in established models of IUGR to understand better the 
      pathophysiological mechanisms linking placental insufficiency with impaired islet 
      development and beta-cell function.
CI  - (c) 2017 Society for Endocrinology.
FAU - Boehmer, Brit H
AU  - Boehmer BH
AD  - Department of PediatricsPerinatal Research Center, University of Colorado School 
      of Medicine, Aurora, Colorado, USA.
FAU - Limesand, Sean W
AU  - Limesand SW
AD  - School of Animal and Comparative Biomedical SciencesUniversity of Arizona, 
      Tucson, Arizona, USA.
FAU - Rozance, Paul J
AU  - Rozance PJ
AD  - Department of PediatricsPerinatal Research Center, University of Colorado School 
      of Medicine, Aurora, Colorado, USA paul.rozance@ucdenver.edu.
LA  - eng
GR  - R01 DK084842/DK/NIDDK NIH HHS/United States
GR  - R01 DK088139/DK/NIDDK NIH HHS/United States
GR  - T32 HD007186/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20170814
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
SB  - IM
MH  - Female
MH  - Fetal Growth Retardation/*pathology
MH  - Humans
MH  - Infant, Newborn
MH  - Insulin-Secreting Cells/*physiology
MH  - Islets of Langerhans/*growth & development
MH  - Placental Insufficiency/physiopathology
MH  - Pregnancy
PMC - PMC5808569
MID - NIHMS937997
OTO - NOTNLM
OT  - IUGR
OT  - islet
OT  - pancreas
OT  - beta-cell
COIS- Declaration of interest The authors declare that there are no conflicts of 
      interest.
EDAT- 2017/08/16 06:00
MHDA- 2017/09/26 06:00
PMCR- 2018/02/12
CRDT- 2017/08/16 06:00
PHST- 2017/07/27 00:00 [received]
PHST- 2017/08/10 00:00 [accepted]
PHST- 2017/08/16 06:00 [pubmed]
PHST- 2017/09/26 06:00 [medline]
PHST- 2017/08/16 06:00 [entrez]
PHST- 2018/02/12 00:00 [pmc-release]
AID - JOE-17-0076 [pii]
AID - 10.1530/JOE-17-0076 [doi]
PST - ppublish
SO  - J Endocrinol. 2017 Nov;235(2):R63-R76. doi: 10.1530/JOE-17-0076. Epub 2017 Aug 
      14.