PMID- 34884717
OWN - NLM
STAT- MEDLINE
DCOM- 20220112
LR  - 20220112
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 23
DP  - 2021 Nov 29
TI  - Acetone Ingestion Mimics a Fasting State to Improve Glucose Tolerance in a Mouse 
      Model of Gestational Hyperglycemia.
LID - 10.3390/ijms222312914 [doi]
LID - 12914
AB  - Gestational diabetes mellitus results, in part, from a sub-optimal beta-cell mass 
      (BCM) during pregnancy. Artemisinins were reported to increase BCM in models of 
      diabetes by alpha- to beta-cell conversion leading to enhanced glucose tolerance. We 
      used a mouse model of gestational glucose intolerance to compare the effects of 
      an artemisinin (artesunate) on glycemia of pregnant mice with vehicle treatment 
      (acetone) or no treatment. Animals were treated daily from gestational days (GD) 
      0.5 to 6.5. An intraperitoneal glucose tolerance test was performed prior to 
      euthanasia at GD18.5 or post-partum. Glucose tolerance was significantly improved 
      in both pregnant and non-pregnant mice with both artesunate and vehicle-alone 
      treatment, suggesting the outcome was primarily due to the acetone vehicle. In 
      non-pregnant, acetone-treated animals, improved glucose tolerance was associated 
      with a higher BCM and a significant increase in bihormonal insulin and 
      glucagon-containing pancreatic islet cells, suggesting alpha- to beta-cell conversion. 
      BCM did not differ with treatment during pregnancy or post-partum. However, 
      placental weight was higher in acetone-treated animals and was associated with an 
      upregulation of apelinergic genes. Acetone-treated animals had reduced weight 
      gain during treatment despite comparable food consumption to non-treated mice, 
      suggesting transient effects on nutrient uptake. The mean duodenal and ileum 
      villus height was reduced following exposure to acetone. We conclude that acetone 
      treatment may mimic transient fasting, resulting in a subsequent improvement in 
      glucose tolerance during pregnancy.
FAU - Szlapinski, Sandra
AU  - Szlapinski S
AUID- ORCID: 0000-0002-2698-7224
AD  - Lawson Health Research Institute, St. Joseph Health Care, London, ON N6A 4V2, 
      Canada.
AD  - Department of Physiology and Pharmacology, Western University, London, ON N6A 
      3K7, Canada.
FAU - Strutt, Brenda
AU  - Strutt B
AD  - Lawson Health Research Institute, St. Joseph Health Care, London, ON N6A 4V2, 
      Canada.
FAU - Deane, Madeline
AU  - Deane M
AD  - Lawson Health Research Institute, St. Joseph Health Care, London, ON N6A 4V2, 
      Canada.
AD  - Molecular Biology and Genetics Program, Faculty of Science, McMaster University, 
      Hamilton, ON L8S 4LD, Canada.
FAU - Arany, Edith
AU  - Arany E
AD  - Lawson Health Research Institute, St. Joseph Health Care, London, ON N6A 4V2, 
      Canada.
AD  - Department of Physiology and Pharmacology, Western University, London, ON N6A 
      3K7, Canada.
AD  - Departments of Pathology and Laboratory Medicine, Western University, London, ON 
      N6A 3K7, Canada.
AD  - Department of Medicine, Western University, London, ON N6A 3K7, Canada.
FAU - Bennett, Jamie
AU  - Bennett J
AD  - Lawson Health Research Institute, St. Joseph Health Care, London, ON N6A 4V2, 
      Canada.
AD  - Life Sciences Program, School of Interdisciplinary Science, McMaster University, 
      Hamilton, ON L8S 4LD, Canada.
FAU - Hill, David J
AU  - Hill DJ
AUID- ORCID: 0000-0002-2490-5678
AD  - Lawson Health Research Institute, St. Joseph Health Care, London, ON N6A 4V2, 
      Canada.
AD  - Department of Physiology and Pharmacology, Western University, London, ON N6A 
      3K7, Canada.
AD  - Departments of Paediatrics, Western University, London, ON N6A 3K7, Canada.
LA  - eng
GR  - MOP-15263/CAPMC/CIHR/Canada
GR  - no number/Alan Thicke Centre for Juvenile Diabetes Research/
PT  - Journal Article
DEP - 20211129
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antimalarials)
RN  - 0 (Apelin)
RN  - 1364PS73AF (Acetone)
RN  - 60W3249T9M (Artesunate)
SB  - IM
MH  - Acetone/*pharmacology
MH  - Animals
MH  - Antimalarials/*therapeutic use
MH  - Apelin/metabolism
MH  - Artesunate/*therapeutic use
MH  - Diabetes, Gestational/*drug therapy
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Fasting
MH  - Female
MH  - Intestines/drug effects
MH  - Pancreas/*drug effects
MH  - Placenta/drug effects/metabolism
MH  - Pregnancy
MH  - Pregnancy Outcome
PMC - PMC8657850
OTO - NOTNLM
OT  - acetone
OT  - artemisinin
OT  - glycemia
OT  - islet of Langerhans
OT  - pancreas
OT  - pregnancy
OT  - beta-cell
COIS- The study funders were not involved in the design of the study; the collection, 
      analysis, and interpretation of data; or the writing of the report; and did not 
      impose any restrictions regarding the publication of the report. The authors had 
      no financial or professional conflicts of interest with the funding agencies.
EDAT- 2021/12/11 06:00
MHDA- 2022/01/13 06:00
PMCR- 2021/11/29
CRDT- 2021/12/10 01:04
PHST- 2021/10/06 00:00 [received]
PHST- 2021/11/23 00:00 [revised]
PHST- 2021/11/27 00:00 [accepted]
PHST- 2021/12/10 01:04 [entrez]
PHST- 2021/12/11 06:00 [pubmed]
PHST- 2022/01/13 06:00 [medline]
PHST- 2021/11/29 00:00 [pmc-release]
AID - ijms222312914 [pii]
AID - ijms-22-12914 [pii]
AID - 10.3390/ijms222312914 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Nov 29;22(23):12914. doi: 10.3390/ijms222312914.