Date of Graduation
School of Medicine
Randall W. Bryner
Paul D. Chantler
Paul D. Chantler
I. Mark Olfert
Obesity is concomitant with hyperglycemic conditions, increased proinflammatory cytokines, and increased oxidative stress. Under hyperglycemia, thioredoxin interacting protein (TXNIP) is increased and causes increased oxidative stress and pancreatic b-cell apoptosis. Chronic stress is associated with increased glucocorticoid levels and a proinflammatory environment. The purpose of this study was to examine the effects of obesity, chronic stress, and exercise on pancreatic health.
Lean Zucker Rats (LZRs) and Obese Zucker Rats (OZRs) were randomly assigned to four groups: 1) sedentary controls (C: n=8 per); 2) unpredictable chronic mild stress (UCMS) (S: n=8); 3) exercise (E: n=8); and 4) combined UCMS and exercise (ExS: n=8). Exercise rats underwent 8 weeks of treadmill running for 60 minutes. Stress rats were subjected to UCMS that included cage tilt, no bedding, damp bedding, bath, social stress, and altered light-dark cycles for 8 hours a day, 5 days a week for 8 weeks. Pancreas tissue was obtained from rats around 20 weeks of age. Total pancreatic TXNIP protein was quantified, including total pancreatic cytokine expression for IL-1b, TNF-a, IL-4, and IL-10. Using immunohistochemistry, b-cell and a-cell counting, islet area measurements, and b-cell to a-cell ratio were examined. TUNEL staining, to determine apoptosis, was examined in pancreatic lysates.
OZRs had higher insulin, glucose, and body mass compared to LZRs, as wells as higher b-cell and a-cell number and islet area (p
In a model of obesity and metabolic syndrome, the pancreas appeared to be stimulated to grow as indicated by greater numbers of β- and α-cells and larger islets even in the presence of slightly higher pancreatic TXNIP and TNF-α. Obesity resulted in an increased level of inflammation and reduced antioxidant potential within the pancreas as indicated by significantly higher TXNIP, IL-1b, and TNF-a. Eight weeks of treadmill running reversed this effect. Exercise training was also able to reduced TXNIP within the pancreas as a result of stress.
Tice, Abigail, "The Effects of Obesity, Chronic Stress, and Exercise on Pancreatic Health" (2019). Graduate Theses, Dissertations, and Problem Reports. 4034.