Endocrinology Commons^™

Novel Regulators Of Small G Proteins In The Pancreatic Beta Cell, Noah Gleason

Wayne State University Dissertations

Regulation of small GTPases within the pancreatic beta cell is a highly complex and coordinated sequence of protein interactions and post translational modifications. Various families participate in the physiological secretion of insulin in roles ranging from cytoskeletal reorganization to secretory vesicle priming and docking. However the regulatory partners of GTPase function, while studied broadly, lack vital information relating to smgGDS, a protein chaperone of small GTPases to and from the prenylation machinery, and RhoGDI function. Herein these studies are aimed to further our understanding of GTPase regulation and alterations that occur during metabolic stress (glucotoxicity) and related beta cell dysfunction.Data …

Mixed-Lineage Kinase-3 (Mlk3) Plays A Negative Modulatory Role In Insulin Secretion From The Pancreatic Β-Cell, Tyler Russeth, Vijayalakshmi Thamilselvan, Anjaneyulu Kowluru

Medical Student Research Symposium

Glucose-stimulated insulin secretion (GSIS) from the pancreatic β-cell in response to elevated levels of glucose is controlled by a variety of signals including intracellular calcium and nucleotides such as cAMP, ATP and GTP. These cellular signals are responsible for activation of specific kinases that mediate phosphorylation of key exocytotic proteins that lead to GSIS. In the context of protein kinases, mixed-lineage kinases (MLKs) have been implicated in an assortment of cellular functions, including cell proliferation and apoptosis. However, very little is known on potential regulatory roles of MLKs in islet β-cell function, including GSIS. The goal of this study is …

Testosterone And Interpersonal Attraction: A Placebo-Controlled Design, Stefan M. Goetz

Wayne State University Dissertations

Testosterone has long been implicated as a neuroendocrinological mechanism in the expression of reproductive strategies. Humans the world over form and maintain pair-bonds suggesting that pair-bonds may serve to enhance reproductive fitness. However, infidelity is a perennial threat to these bonds. The data in humans suggests that testosterone is associated with mate-seeking but may be detrimental to relationship maintenance. However, past work has relied on correlational studies and additional findings from nonhuman animal models suggest that acute changes rather than baseline concentrations in testosterone may in fact protect extant pair-bonds. The present research sought to test the causal role of …

Crebh, A Novel Liver Clock Keeper For Energy Metabolism, Ze Zheng

Wayne State University Dissertations

Circadian rhythms play crucial roles in orchestrating diverse physiological processes that are critical for health and disease. Cyclic AMP responsive element binding protein 3-like 3 (CREB3L3, also known as CREBH) is a liver-enriched, endoplasmic reticulum (ER)-tethered transcription factor known to regulate hepatic acute-phase response and energy homeostasis under stress conditions. Here, we demonstrate that CREBH is regulated by the circadian clock and functions as a diurnal regulator of hepatic lipid and glucose metabolism. CREBH is required to maintain circadian profiles of blood triglycerides, fatty acids, and glucose as well as hepatic glycogen storage. CREBH rhythmically regulates expression levels and amplitudes …

Self-Construal Moderates Testosterone Reactivity To Competitive Outcomes, Keith Welker

Wayne State University Dissertations

Previous research shows that testosterone reactivity to competitive outcomes predicts aggressive behavior in men. However, some studies have failed to find these effects, and it has been suggested that individual differences moderate the relationships between competitive outcomes, testosterone fluctuations, and aggressive behavior. The current research examined whether one individual difference--self-construal--would moderate these effects. In Study 1, participants were assigned to win or lose a competitive video game and engaged in a reactive aggression task. Results indicated that increases in testosterone in response to winning and decreases in response to losing occurred in men with independent, not interdependent, self-construals. These changes …

Fatty Acid Fate In Determining Oxidation And Inflammation In Adipose Tissue, Emilio Patrick Mottillo

Wayne State University Dissertations

Adipose tissue (AT) is a critical regulator of energy balance through its ability to store or oxidize free fatty acids (FFAs). White adipose tissue (WAT) functions as an anabolic organ to sequester and release FAs, in contrast brown adipose tissue (BAT) is a catabolic organ that oxidizes FAs. However, a comprehensive understanding of the role that FFAs play in the function of WAT and BAT is needed. Here we demonstrate that intracellular FAs enhance the expression of inflammatory cytokines by β3-AR activation in adipocytes, in which the expression of PAI-1 is partly mediated by the de novo synthesis of ceramides/sphingolipids. …

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …