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    3T3-L1 adipocytes as a model of Glut4 translocation

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    Author
    Collin, Aline
    Chair
    Duffy, Lawrence
    Committee
    Coker, Robert
    Coker, Melynda Sheri
    Drew, Kelly
    Keyword
    Glucose
    Fat cells
    Metabolism
    Adipose tissues
    Diabetes
    Pathophysiology
    Insulin resistance
    Bog blueberry
    Nutrition
    Health
    Sled dogs
    Exercise
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    URI
    http://hdl.handle.net/11122/12992
    Abstract
    Type 2 diabetes (T2D), a lethal disease, reveals an alarming increase of epidemic proportions and, by 2050, an estimated 1 in 3 adults in the US will suffer from it. Persistent and systemic inflammatory and oxidative stress in adipose tissue and skeletal muscle are recognized as key players in the progression of T2D. T2D is characterized by insulin resistance, the inability of cells to respond to standard circulating levels of insulin, resulting in hyperglycemia. In adipocytes and skeletal muscle, glucose uptake, a vital step in blood glucose regulation, predominantly occurs via the glucose transporter 4 (Glut4) in an insulindependent recruitment from a cytosolic vesicle. Under inflammatory stress, these cells have demonstrated a lack of Glut4 presence in the plasma membrane, leading to a lack of glucose transport within these cells. 3T3-L1 murine adipocytes are a key model to study insulin signaling in vitro. Mature adipocytes are converted from fibroblasts in a lengthy process requiring chemical induction. Several inducers have been tested in hopes to shorten the time span required for differentiation. However, the use of different inducers and changes in the differentiation programming could have consequences on the phenotype of the mature adipocytes. For this reason, we sought to evaluate the differences in 3T3-L1 fibroblasts induced with either 3-isobutyl-1-methylxanthine (IBMX), or troglitazone. In addition to pharmaceutical recourse to restore insulin signaling and glucose uptake in cells under inflammatory duress, a dietary approach has been considered. Natural products such as blueberries have been of particular interest due to their health benefit including antioxidant benefits and their ability to modulate biochemical pathways. Wild Alaskan blueberries are of particular interest due to their link to a reduced prevalence of T2D in Alaskan Native populations. Here, we report differences in the phenotype of 3T3-L1 adipocytes based on the inducer of adipogenesis and a lack of increase in plasma membrane Glut4. Our studies demonstrate a higher expression of adipocyte biomarkers in cells treated with troglitazone compared to IBMX, but a higher expression of total Glut4 in cells treated with IBMX compared to troglitazone. In both phenotypes, we note a lack of insulin-induced increase of plasma membrane levels of Glut4 in 3T3-L1 mature adipocytes. Finally, we demonstrate an insulin-like benefit of Alaskan blueberry extracts on plasma membrane Glut4.
    Description
    Dissertation (Ph.D.) University of Alaska Fairbanks, 2021
    Table of Contents
    Chapter 1: General introduction -- Chapter 2. IBMX and troglitazone induce 3T3-L1 adipocytes of different phenotype -- Chapter 3. Alaskan blueberries positively affect Glut4 translocation -- Chapter 4: Bioavailability of Alaskan blueberry extracts: an in vitro approach -- Chapter 5. Weight gain, conditioning and metabolic syndrome: a sled dog model -- Chapter 6: General conclusions.
    Date
    2021-12
    Type
    Dissertation
    Collections
    Chemistry and Biochemistry

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