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The Role of Selenocysteine Lyase in Pancreatic Islet Physiology and its Sex-Specific Regulation of Energy Metabolism.

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Title:The Role of Selenocysteine Lyase in Pancreatic Islet Physiology and its Sex-Specific Regulation of Energy Metabolism.
Authors:Ogawa-Wong, Ashley N.
Contributors:Cell & Molecular Biology (department)
metabolic disease
Date Issued:Aug 2017
Publisher:University of Hawaiʻi at Mānoa
Abstract:Obesity is a symptom of metabolic syndrome, a condition that increases lifetime risk of type 2 diabetes and cardiovascular disease. Proper maintenance of the insulin producing β-cells are necessary for glucose homeostasis. Although glucose is the most important nutrient factor involved in insulin secretion, we are increasingly becoming aware of the role of trace elements such as selenium (Se) in β-cell function. Previously, we reported that the putative Se recycling enzyme selenocysteine lyase (Scly) may be involved in regulating lipid and carbohydrate metabolism. Scly-/- mice develop a remarkable increase in fasting hyperinsulinemia, warranting further investigation into the role of Scly in β-cells. Moreover, we described possible sex differences in Scly regulation of energy metabolism. The experiments in the first aim focused on the role of Scly in pancreatic islet function. Immunofluorescent imaging studies were employed to confirm Scly expression in the pancreatic islet. Glucose-stimulated insulin secretion was increased in the absence of Scly-/- in the β-cell-like MIN6 cells but slightly impaired in isolated pancreatic islets, indicating Scly may influence islet paracrine signaling. Neither islet selenoprotein expression nor sulfur pathway enzyme gene expression were altered when Scly is deleted. While Scly is expressed in the islet and its deletion in vivo results in hyperinsulinemia, further studies are necessary to determine the mechanistic role of Scly in islet function. The second aim built upon previous observations that the role of Scly in energy metabolism may be sex-specific. Female Scly-/- mice were found to exhibit increased body fat composition when compared to their WT counterparts, but they were protected from impairments in insulin signaling. Castration was not sufficient to rescue adiposity or energy expenditure, but restored fasting insulin to WT levels in the male Scly-/- mice. Interestingly, reduced hypothalamic selenoprotein expression in male and female Scly-/- mice suggest Scly
may regulate lipid metabolism indirectly through maintaining hypothalamic function, indicating a novel role for Scly as a key regulator in the brain-fat axis.
Description:Ph.D. Thesis. University of Hawaiʻi at Mānoa 2017.
Rights:All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
Appears in Collections: Ph.D. - Cell and Molecular Biology

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