Browsing by Author "Fullenkamp, Allison M."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Effect of different obesogenic diets on pancreatic histology in Ossabaw miniature swine
    (Wolters Kluwer, 2011-04) Fullenkamp, Allison M.; Bell, Lauren N.; Robbins, Reiesha D.; Lee, Lydia; Saxena, Romil; Alloosh, Mouhamad; Klaunig, James E.; Mirmira, Raghavendra G.; Sturek, Michael; Chalasani, Naga; Department of Medicine, IU School of Medicine
    OBJECTIVE: Obesity is a factor in the outcome and severity of pancreatic conditions. We examined the effect of hypercaloric diets on the pancreata of Ossabaw swine, a large animal model of metabolic syndrome and obesity. METHODS: Swine were fed with 1 of 4 diets: high-fructose (n = 9), atherogenic (n = 10), modified atherogenic (n = 6), or eucaloric standard diet (n = 12) for 24 weeks. Serum chemistries were measured, and pancreata were examined for histological abnormalities including steatosis, inflammation or fibrosis, insulin content, and oxidative stress. RESULTS: The fructose, atherogenic, and modified atherogenic diet groups exhibited obesity, metabolic syndrome, islet enlargement, and significantly increased pancreatic steatosis (22.9% ± 7.5%, 19.7% ± 7.7%, and 38.7% ± 15.3% fat in total tissue area, respectively) compared with controls (9.3% ± 1.9%; P < 0.05). The modified atherogenic diet group showed significantly increased oxidative stress levels as evidenced by elevated serum malondialdehyde (3.0 ± 3.3 vs 1.5 ± 0.3 μmol/L in controls; P = 0.006) and pancreatic malondialdehyde (0.1 ± 0.12 vs 0.04 ± 0.01 nmol/mg protein in controls; P = 0.01). None of the swine exhibited pancreatitis or cellular injury. CONCLUSIONS: Ossabaw swine fed with a modified atherogenic diet developed significant pancreatic steatosis and increased oxidative stress, but no other histological abnormalities were observed.
  • Thumbnail Image
    Item
    Metabolic Syndrome Abolishes Glucagon-Like Peptide 1 Receptor Agonist Stimulation of SERCA in Coronary Smooth Muscle
    (American Diabetes Association, 2015-09) Dineen, Stacey L.; McKenney, Mikaela L.; Bell, Lauren N.; Fullenkamp, Allison M.; Schultz, Kyle A.; Alloosh, Mouhamad; Chalasani, Naga; Sturek, Michael; Department of Cellular & Integrative Physiology, IU School of Medicine
    Metabolic syndrome (MetS) doubles the risk of adverse cardiovascular events. Glucagon-like peptide 1 (GLP-1) receptor agonists induce weight loss, increase insulin secretion, and improve glucose tolerance. Studies in healthy animals suggest cardioprotective properties of GLP-1 receptor agonists, perhaps partially mediated by improved sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA) activity. We examined the acute effect of GLP-1 receptor agonists on coronary smooth muscle cells (CSM) enzymatically isolated from lean, healthy Ossabaw miniature swine. Intracellular Ca(2+) handling was interrogated with fura-2. The GLP-1 receptor agonist exenatide activated SERCA but did not alter other Ca(2+) transporters. Further, we tested the hypothesis that chronic, in vivo treatment with GLP-1 receptor agonist AC3174 would attenuate coronary artery disease (CAD) in swine with MetS. MetS was induced in 20 swine by 6 months' feeding of a hypercaloric, atherogenic diet. Swine were then randomized (n = 10/group) into placebo or AC3174 treatment groups and continued the diet for an additional 6 months. AC3174 treatment attenuated weight gain, increased insulin secretion, and improved glucose tolerance. Intravascular ultrasound and histology showed no effect of AC3174 on CAD. MetS abolished SERCA activation by GLP-1 receptor agonists. We conclude that MetS confers vascular resistance to GLP-1 receptor agonists, partially through impaired cellular signaling steps involving SERCA.