PMID- 33231513
OWN - NLM
STAT- MEDLINE
DCOM- 20210921
LR  - 20240226
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 246
IP  - 5
DP  - 2021 Mar
TI  - Increased alpha and beta cell mass during mouse pregnancy is not dependent on 
      transdifferentiation.
PG  - 617-628
LID - 10.1177/1535370220972686 [doi]
AB  - Maternal pancreatic beta-cell mass (BCM) increases during pregnancy to compensate 
      for relative insulin resistance. If BCM expansion is suboptimal, gestational 
      diabetes mellitus can develop. Alpha-cell mass (ACM) also changes during 
      pregnancy, but there is a lack of information about alpha-cell plasticity in 
      pregnancy and whether alpha- to beta-cell transdifferentiation can occur. To investigate 
      this, we used a mouse model of gestational glucose intolerance induced by feeding 
      low-protein (LP) diet from conception until weaning and compared pregnant female 
      offspring to control diet-fed animals. Control and LP pancreata were collected 
      for immunohistochemical analysis and serum glucagon levels were measured. In 
      order to lineage trace alpha- to beta-cell conversion, we utilized transgenic mice 
      expressing yellow fluorescent protein behind the proglucagon gene promoter 
      (Gcg-Cre/YFP) and collected pancreata for histology at various gestational 
      timepoints. Alpha-cell proliferation increased significantly at gestational day 
      (GD) 9.5 in control pregnancies resulting in an increased ACM at GD18.5, and this 
      was significantly reduced in LP animals. Despite these changes, serum glucagon 
      was higher in LP mice at GD18.5. Pregnant Gcg-Cre/YFP mice showed no increase in 
      the abundance of insulin(+)YFP(+)glucagon(-) cells (phenotypic beta-cells). A second 
      population of insulin(+)YFP(+)glucagon(+) cells was identified which also did not 
      alter during pregnancy. However, there was an altered anatomical distribution 
      within islets with fewer insulin(+)YFP(+)glucagon(-) cells but more 
      insulin(+)YFP(+)glucagon(+) cells being present in the islet mantle at GD18.5. 
      These findings demonstrate that dynamic changes in ACM occur during normal 
      pregnancy and were altered in glucose-intolerant pregnancies.
FAU - Szlapinski, Sandra K
AU  - Szlapinski SK
AUID- ORCID: 0000-0002-2698-7224
AD  - Department of Physiology and Pharmacology, Western University, London, ON N6A 
      3K7, Canada.
AD  - Lawson Health Research Institute, Diabetes & Endocrinology, St Joseph's Health 
      Care, London, ON N6A 4V2, Canada.
FAU - Bennett, Jamie
AU  - Bennett J
AD  - Lawson Health Research Institute, Diabetes & Endocrinology, St Joseph's Health 
      Care, London, ON N6A 4V2, Canada.
FAU - Strutt, Brenda J
AU  - Strutt BJ
AD  - Department of Physiology and Pharmacology, Western University, London, ON N6A 
      3K7, Canada.
AD  - Lawson Health Research Institute, Diabetes & Endocrinology, St Joseph's Health 
      Care, London, ON N6A 4V2, Canada.
FAU - Hill, David J
AU  - Hill DJ
AD  - Department of Physiology and Pharmacology, Western University, London, ON N6A 
      3K7, Canada.
AD  - Lawson Health Research Institute, Diabetes & Endocrinology, St Joseph's Health 
      Care, London, ON N6A 4V2, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201124
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Insulin)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Animals
MH  - Cell Proliferation
MH  - *Cell Transdifferentiation
MH  - Female
MH  - Glucagon/blood/metabolism
MH  - Glucagon-Secreting Cells/*cytology/metabolism
MH  - Glucose Intolerance/pathology
MH  - Insulin/blood/metabolism
MH  - Insulin-Secreting Cells/*cytology/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Pregnancy
MH  - Mice
PMC - PMC7934144
OTO - NOTNLM
OT  - Pancreas
OT  - alpha-cell
OT  - beta-cell
OT  - gestational diabetes
OT  - mouse
OT  - pregnancy
COIS- Declaration of conflicting interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2020/11/25 06:00
MHDA- 2021/09/22 06:00
PMCR- 2022/03/01
CRDT- 2020/11/24 12:10
PHST- 2020/11/25 06:00 [pubmed]
PHST- 2021/09/22 06:00 [medline]
PHST- 2020/11/24 12:10 [entrez]
PHST- 2022/03/01 00:00 [pmc-release]
AID - 10.1177_1535370220972686 [pii]
AID - 10.1177/1535370220972686 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2021 Mar;246(5):617-628. doi: 10.1177/1535370220972686. 
      Epub 2020 Nov 24.