191-LB: Artesunate Treatment Improves Hyperglycemia in a Rodent Model of Gestational Glucose Intolerance without Increasing Beta-Cell Mass

Abstract

Gestational diabetes (GDM) has been associated with a failure to adequately increase maternal β-cell mass (BCM) during pregnancy. The anti-malarial drugs, artemisinins, have been shown to improve glucose homeostasis in rodent models of diabetes by increasing BCM. Our objective was to reverse BCM deficiency and impaired glucose tolerance in a mouse model of GDM using the artemisinin artesunate. In order to produce glucose intolerance in pregnancy, female mice (F0) were fed a low protein (8%, LP) diet during gestation and lactation, and offspring weaned onto control (20%, C) diet. At 6-10 weeks age female offspring (F1) were time-mated and given C diet throughout pregnancy. Artesunate was administered via drinking water from gestational day (GD) 0.5-6.5. We previously found glucose intolerance, mimicking aspects of GDM, in LP-exposed offspring at GD18 when compared to animals fed a C diet. Thus, glucose tolerance tests (GTT) were performed at GD18 or for non-pregnant age-matched animals. Subsequently, pancreata were removed for fluorescence immunohistochemistry to assess histology. Artesunate-treated LP females had a lower area under the curve during a GTT (389.9±52.3mmol/L*min) compared to non-treated LP females at GD18 (726.6±56.9mmol/L*min, p<0.01). Furthermore, artesunate-treated LP females had improved glucose homeostasis at 5min (9.1 vs. 18.9mmol/L), 15min (11.6 vs. 20.9mmol/L) and 30min (10.2 vs. 19.2mmol/L) during the GTT compared to non-treated LP females at GD18 (p<0.05). There were no significant differences in BCM, alpha-cell mass, or mean islet size between LP and artesunate-treated LP females at GD18. The results show that artesunate-treated LP pregnant females had significantly improved glucose homeostasis compared to untreated LP mice at GD18. However, the improved glucose tolerance was not associated with increased BCM or changes in endocrine pancreas morphology. Disclosure S. Szlapinski: None. D.J. Hill: None. Funding St. Joseph's Health Care Foundation; Ontario Graduate Scholarship