Abstract
Gestational diabetes mellitus results, in part, from a sub-optimal β-cell mass (BCM) during pregnancy. Artemisinins were reported to increase BCM in models of diabetes by α- to β-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 α- to β-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.
Highlights
We examined pregnant mice previously exposed to a maternal low protein (LP) diet during pregnancy and lactation as a model of glucose intolerance during and following pregnancy [12]
Maternal weight gain was significantly lower in both artesunate/acetone and the acetone vehicle group alone compared to non-treated animals (Figure 1A)
The initial objective of testing artesunate was negated as we noted that the improvement in glucose tolerance was similar between the treatment group of artesunate diluted in acetone vehicle and that of the vehicle alone, leading us to conclude that the effect was primarily due to administration of the acetone vehicle
Summary
Insulin resistance is a normal physiological feature in the third trimester of pregnancy that requires compensatory adaptations to occur within the maternal endocrine pancreas in order to maintain maternal euglycemia [1]. Should this compensation by the pancreatic βcell be sub-optimal, gestational diabetes mellitus (GDM) can develop. The increased BCM resulted in improved glucose homeostasis, suggesting a possible beneficial effect of treatment with artemisinins in animal models of diabetes. Our hypothesis was that treatment with artesunate would improve glucose tolerance during pregnancy, as was observed in previous studies in diabetic mice [21]. We elucidated unexpected mechanisms responsible for improved glucose tolerance unrelated to the presence of an artemisinin
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