Gestational Diabetes Mellitus (GDM) is one of the most common obstetrical complications affecting up to 18% of all pregnancies. Although GDM usually resolves after pregnancy, it is associated with lasting health effects in mother and baby. Due to the transient nature of GDM, good animal models are needed to improve our understanding of the mechanisms regulating GDM and its long-term health effects. We therefore, developed a unique mouse model of GDM, which exhibits numerous characteristics of GDM pathophysiology in human pregnancy including, no diabetes prior to pregnancy, development of diabetes during pregnancy, and resolution of diabetes following pregnancy. Dams exposed to a GDM pregnancy also exhibited glucose intolerance later in life. Further validation of this animal model is warranted in order to establish it as a universal animal model of GDM. The overall aim of this proposal is to further characterize our newly developed animal model of GDM during pregnancy in order to identify potential mechanisms regulating the patho- physiology of GDM. We propose to evaluate insulin resistance and insulin secretion in our animal model further validating our animal model as a useful and unique tool to study the mechanisms regulating the patho- physiology of GDM. Preliminary data from our GDM animal model indicates that pancreatic intra-islet vasculature is impaired in pregnancy. We therefore also propose to examine vascular and beta cell expansion during pregnancy and determine if vascular expansion is impaired prior to beta cell expansion in GDM dams. This further characterization of the timing of decreased pancreatic vascular and beta cell expansion is necessary in order to understand and pursue the potential role of impaired pancreatic vasculature in the manifestation of GDM.
Gestational Diabetes Mellitus (GDM) is one of the most common obstetrical complications and has long term deleterious health effects on mother and baby. The mechanisms regulating GDM and the long term maternal health effects are poorly understood and good animal models are necessary to study these health risks. Work in this proposal further validates our unique animal model to study the patho-physiology of GDM; furthermore this proposal works to characterize the potential and novel role impaired pancreatic vasculature plays in the manifestation of GDM.
