Browsing by Author "Reul, Olivia"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Impact of Diet on the KK-Ay Mouse Model of Type 2 Diabetes
    (2024-05) Reul, Olivia; Wallace, Joseph M.; Allen, Matthew R.; Surowiec, Rachel K.
    Diabetes is an international health crisis with 1 in 10 (537 million) adults worldwide living with diabetes, and type 2 diabetes (T2D) composing 90% of these cases [1]. T2D is a disease characterized by insulin resistance that leads to pancreatic β cell dysfunction and hyperglycemia. It is known to have deleterious effects on various organ systems, including the skeletal system, leading to an increased fracture risk, despite normal or elevated bone mineral density (BMD). Due to this unique facet of T2D, the cause of this elevated fracture risk has recently become an area of focus both in the clinic and in research. One of the primary concerns when researching this disease state is the use of a model capable of mimicking the complex multisystem effects of diabetes, including the skeletal outcomes. The Yellow Kuo Kondo (KK-Ay) mouse model has shown promise as a non-diet dependent obese model of T2D. In this model, mice heterozygous for a mutation in the agouti gene (Ay) are treated as an obese model of T2D (KK-Ay) while those that are homozygous (no mutation) are a non-diabetic obese control [2]. Although previous studies have revealed this model can display the multisystem effects of diabetes [3,4], data suggest that the efficacy of the model may in fact be reliant on diet. To explore this, mice were placed on separate diets, half on a standard chow (LabDiet 5001) diet and the other half on a diet recommended by Jackson Laboratory for this strain (LabDiet 5LG4). Animals were aged to 16 weeks (wks) with blood glucose (BG) and body weight (BW) monitored every other week and glucose tolerance tests (GTT) and insulin tolerance tests (ITT) performed at 15 wks. At 16 wks, animals were sacrificed via cardiac exsanguination to collect whole blood and blood serum followed by cervical dislocation. The pancreas, bilateral tibiae, and bilateral femora were collected from each animal immediately following sacrifice. Diet did in fact have a significant impact on both the skeletal and metabolic phenotype associated with T2D. Results suggest that future studies should employ the 5LG4 diet in heterozygous animals and the 5001 diet in homozygous animals to better explore the impacts of T2D against a non-diabetic control.
  • Thumbnail Image
    Item
    Model for Gold Nanoparticle Synthesis: Effect of pH and Reaction Time
    (American Chemical Society, 2021-06-24) Yazdani, Saeed; Daneshkhah, Ali; Diwate, Abolee; Patel, Hardi; Smith, Joshua; Reul, Olivia; Cheng, Ruihua; Izadian, Afshin; Hajrasouliha, Amir Reza; Physics, School of Science
    The synthesis of gold nanoparticles is dependent on both the concentration of trisodium citrate dihydrate and the time that it interacts with tetrachloroauric acid. A wide range of gold nanoparticles with various sizes and dispersity can be produced based on control variables, such as time of reaction and acid concentration, using a similar approach to that of the Turkevich model. In this model, the pH of the solution decreases slightly throughout the reaction (0.005 unit/min) due to the chemical interactions between trisodium citrate dihydrate and tetrachloroauric acid. Dicarboxy acetone is formed during citrate oxidization, resulting in gold nuclei formation over time. In addition, gold nanoparticle nucleation causes pH fluctuation over time based on gold nanoparticle sizes. An inverse correlation (coefficient of smaller than -0.97) was calculated between the pH and reaction time at different ratios of trisodium citrate dihydrate to tetrachloroauric acid. Regression analysis was used to develop a model for the prediction of the size of gold nanoparticles ranging from 18 to 38 nm based on the concentration of trisodium citrate dihydrate and the reaction time.
  • Thumbnail Image
    Item
    Romosozumab rescues impaired bone mass and strength in a murine model of diabetic kidney disease
    (Elsevier, 2024-05-12) Kohler, Rachel; Segvich, Dyann M.; Reul, Olivia; Metzger, Corinne E.; Allen, Matthew R.; Wallace, Joseph M.; Anatomy, Cell Biology and Physiology, School of Medicine
    As international incidence of diabetes and diabetes-driven comorbidities such as chronic kidney disease (CKD) continue to climb, interventions are needed that address the high-risk skeletal fragility of what is a complex disease state. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mineral density and decrease fracture rates in osteoporotic patients with mild to severe CKD, but its effect on diabetes-weakened bone is unknown. We aimed to test Romo's performance in a model of combined diabetes and CKD. 6-week old male C57BL/6 mice were randomly divided into control (CON) and disease model (STZ-Ad) groups, using a previously established streptozotocin- and adenine-diet-induced model. After 16 weeks of disease induction, both CON and STZ-Ad groups were subdivided into two treatment groups and given weekly subcutaneous injections of 100 μL vehicle (phosphorus buffered saline, PBS) or 10 mg/kg Romo. Mice were euthanized after 4 weeks of treatment via cardiac exsanguination and cervical dislocation. Hindlimb bones and L4 vertebrae were cleaned of soft tissue, wrapped in PBS-soaked gauze and stored at —20C. Right tibiae, femora, and L4s were scanned via microcomputed tomography; tibiae were then tested to failure in 4-pt bending while L4s were compression tested. Romo treatment significantly increased cortical and trabecular bone mass in both STZ-Ad and CON animals. These morphological improvements created corresponding increases in cortical bending strength and trabecular compression strength, with STZ-Ad treated mice surpassing vehicle CON mice in all trabecular mechanics measures. These results suggest that Romo retains its efficacy at increasing bone mass and strength in diabetic kidney disease.