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- All Subjects: Diabetes
- All Subjects: Endothelial Cells
- Creators: Sweazea, Karen
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
- Status: Published
2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing fetal heart development but they warrant revalidation and adjustment. 377 normal fetuses with healthy mothers, 98 normal fetuses with diabetic mothers, and 37 fetuses with cardiomyopathy and diabetic mothers had their cardiac structural dimensions, cardiothoracic ratio, valve flow velocities, and heart rates measured by fetal ECHO in a retrospective chart review. Cardiac features were fitted to linear functions, with respect to gestational age, femur length, head circumference, and biparietal diameter and z-scores were created to model normal fetal growth for all parameters. These z-scores were used to assess what metrics had no difference in means between the normal fetuses of both healthy and diabetic mothers but differed from those diagnosed with cardiomyopathy. It was found that functional metrics like mitral and tricuspid E wave and pulmonary velocity could be important predictors for cardiomyopathy when fitted by gestational age, femur length, head circumference, and biparietal diameter. Additionally, aortic and tricuspid annulus diameters when fitted to estimated gestational age showed potential to be predictors for fetal cardiomyopathy. While the metrics overlapped over their full range, combining them together may have the potential for predicting cardiomyopathy in utero. Future directions of this study will explore creating a classifier model that can predict cardiomyopathy using the metrics assessed in this study.
2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing fetal heart development but they warrant revalidation and adjustment. 377 normal fetuses with healthy mothers, 98 normal fetuses with diabetic mothers, and 37 fetuses with cardiomyopathy and diabetic mothers had their cardiac structural dimensions, cardiothoracic ratio, valve flow velocities, and heart rates measured by fetal ECHO in a retrospective chart review. Cardiac features were fitted to linear functions, with respect to gestational age, femur length, head circumference, and biparietal diameter and z-scores were created to model normal fetal growth for all parameters. These z-scores were used to assess what metrics had no difference in means between the normal fetuses of both healthy and diabetic mothers, but differed from those diagnosed with cardiomyopathy. It was found that functional metrics like mitral and tricuspid E wave and pulmonary velocity could be important predictors for cardiomyopathy when fitted by gestational age, femur length, head circumference, and biparietal diameter. Additionally, aortic and tricuspid annulus diameters when fitted to estimated gestational age showed potential to be predictors for fetal cardiomyopathy. While the metrics overlapped over their full range, combining them together may have the potential for predicting cardiomyopathy in utero. Future directions of this study will explore creating a classifier model that can predict cardiomyopathy using the metrics assessed in this study.
within cells that result in changes in the metabolism of carbohydrates and immune functions.
Ingesting glucocorticoids has also been linked to insulin resistance, a main feature of Type 2
diabetes. Experiments including polymerase chain reaction, western blotting, and glycogen
synthase analysis were conducted to determine if exposure to higher doses of dexamethasone, a
glucocorticoid, induces insulin resistance in cultured rat skeletal muscle via interaction with
thioredoxin-interacting protein (TXNIP). Treatment with dexamethasone was shown to cause
mild increases in TXNIP while a definitive increase or decrease in insulin signaling was unable
to be determined.
Sphingosine-1-phosphate receptors (S1PRs) and their signaling pathways play an important role in mediating vascular health and function. Upon ligand mediated activation, S1PRs 1-5 couple with diverse heterotrimeric G-protein subunits (Gαi, Gαq/11, Gα12/13), initiating multimodal downstream signaling pathways which result in various physiological outcomes in the vasculature, including cell proliferation and migration, barrier integrity preservation or loss, contraction, and inflammation. Specifically, S1PR2 activation has been linked to endothelial activation, barrier integrity loss, and inflammation, whereas S1PR1 activation contributes to barrier integrity preservation, vasodilation, and anti-inflammatory properties. Although the role of S1PRs during pathophysiological conditions such as acute ischemic stroke is under current investigation, the complete S1PR expression profile in the cerebrovasculature following acute ischemic injury has not yet been investigated. Therefore, the present study was aimed to characterize the expression profiles of S1PRs 1-5 in human brain microvascular endothelial cells (HBMECs) and human brain vascular smooth muscle cells (HBVSMCs) following 3h hypoxia plus glucose deprivation (HGD; in vitro ischemic injury) exposure. At the mRNA level, we observed expression of S1PRs 1-5 in HBVSMCs and S1PRs 1-4 in HBMECs. Under basal conditions, we employed real-time RT-PCR and observed that mRNA levels of S1PR1 were highest in expression followed by S1PR3 then S1PR2 in HBMECs. On the other hand, S1PR3 mRNA was the highest followed by S1PR2 then S1PR1 in HBVSMCs. In HBMECs, HGD exposure increased S1PR1 mRNA and protein levels, but decreased S1PR1 mRNA in HBVSMCs. Similarly, HGD induced increased S1PR3 mRNA in HBMECs and decreased S1PR3 mRNA in HBVSMCs. For S1PR2, HGD did not alter mRNA or protein expression in HBMECs but increased mRNA levels in HBVSMCs. These data suggest that acute exposure to HGD appears to differentially regulate expression of S1PRs in HBMECs and HBVSMCs. The differential expression in S1PRs both basally and following HGD exposure may suggest distinct signaling mechanisms at play within the two cerebrovascular cell types, implicating these receptors as potential therapeutic targets following ischemic injury.
Birds naturally have high circulating blood glucose concentrations compared to other vertebrates. Several mechanisms have been proposed to explain their high levels including the lack of an insulin responsive glucose transport protein, higher circulating glucagon concentrations, as well as a reliance on lipid oxidation to fuel the high metabolic demands for flight. We suspected the latter may result in the production of the gluconeogenic precursor, glycerol. Therefore, we examined the hypothesis that gluconeogenesis, via glycerol, contributes to the naturally high glucose concentrations in birds (Madiraju et al., 2014). We captured seven mourning doves, Zenaida macroura, in Tempe, AZ, USA and acclimated the birds to captivity for two weeks. In this crossover design study, doves received either an oral inhibitor of gluconeogenesis (150 or 300 mg/kg metformin) or water (50 ul) each week. We measured blood glucose concentrations using a glucometer at baseline, 30, 60 and 120 minutes following the oral dose. In contrast to mammals and chickens, 300 mg/kg metformin did not alter blood glucose (p>0.05) and 150 mg/kg metformin significantly increased blood glucose concentrations (p=0.043) compared to the oral bolus of water. To examine whether the low dose of metformin stimulated glycogenolysis, thus causing the hyperglycemic effect, we administered the low dose of metformin along with an inhibitor of glycogenolysis, 2.5 mg/kg 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), which prevented the hyperglycemic response (p>0.05 vs. water). These data suggest that low doses of metformin activate glycogenolysis. It is possible that glycogenolysis is also activated at the higher dose, but glycogen may be depleted early on resulting in no measurable changes, given the present study design. In conclusion, and in contrast to the hypothesis, mourning doves may not rely on gluconeogenesis to maintain their naturally high blood glucose concentrations under fed conditions, although further studies with more specific gluconeogenic antagonists and under fasted conditions may be needed to confirm these findings.