Date of Graduation

2017

Document Type

Thesis

Degree Type

MS

College

School of Medicine

Department

Physiology, Pharmacology & Neuroscience

Committee Chair

Randy W Bryner

Committee Co-Chair

Stanley M Hileman

Committee Member

I M Olfert

Abstract

Traditional cigarette usage has been linked to a number of nefarious metabolic effects, including insulin resistance; however, the effects of electronic cigarettes (E-cigs) are not currently known. Advertised as a safe alternative for traditional tobacco cigarettes, E-cigs still contain some of the same harmful chemicals as tobacco cigarettes. Through this study, we hope to gain perspective on whether e-cigs play into the development of altered glucose homeostasis. C57BL/6 mice were divided between E-cig (n=15) and control (n=15) groups and exposed to either cappuccino flavored E-cig vapor or filtered air for 4 h/d, 5 d/wk for 8 months. Fasting blood glucose (FBG) and glucose tolerance were observed after 6 months of exposure. Glucose was administered either orally or IP at 2g glucose/kg body mass. Following an overnight fast, an oral glucose tolerance test (OGTT) was performed prior to E-cig exposure; on a separate day another OGT was performed immediately after a 4-hour exposure period. In addition, an intraperitoneal glucose tolerance test (IPGTT) was performed immediately after a 4-hour exposure period in a subset of mice (N=4).;At the conclusion of 8 months of exposure, pancreas tissue was harvested and assessed in a subset of mice (n=6). Total body mass was similar between E-cig and air exposed groups at six months (E-cig: 28.7 +/-1.1g vs Control: 28.8 +/-1.45g) and eight months (E-cig: 29.5+/-1.62g vs Control: 28.9+/-1.06g). FBG prior to E-cig exposure tended to be higher in E-cig vs control mice (p=.13), while glucose following exposure were increased in the E-cig group (143.8+/-6mg/dL vs. 118.8+/-8mg/dL, p=0.05). During the IPGTT, E-cig animals presented with a higher peak blood glucose (225+/-7mg/dL vs. 180+/-15mg/dL, p=0.03), as well as a higher total area under the curve (AUC) than controls (18228 +/- 742 vs 15069 +/- 667 respectively, p=0.02). E-cig animals did not have a different ?-cell density, insulin positive area, or number of SIRT1(+) nuclei. However, SIRT1 density (determined by number of SIRT1(+) nuclei/islet area) was lower in E-cig mice versus control (E-cig: 2.8E-4 +/- 5.0E-5 nuclei/?m vs Controls: 4.4E-4 +/- 5.0E-5 nuclei/?m, p=0.05). Total SIRT1 (E-cig: 1449 +/- 301ng vs Control: 1297 +/- 251ng) and UCP2 (E-cig: 0.08 +/- 0.009 vs. Control: 0.10 +/- 0.01, AU) protein in the pancreas was not different between groups. In conclusion, chronic exposure to E-cig vapor resulted in modestly higher resting and stimulated blood glucose. Although total pancreatic SIRT1 protein levels were not affected, the density of SIRT1 positive ?-cells was reduced in E-cig animals. Future research needs to determine if other pancreatic proteins and mechanisms are negatively affected because of E-cig exposure.

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