<p>Previous studies suggest that nicotine impairs pancreatic function, which may explain the increased risk of T2DM in smokers. We have previously shown that nicotine exposure results in decreased beta cell function, an effect which appears to be mediated via increased beta cell oxidative stress. The goal of this study is to determine whether folic acid, an antioxidant, can prevent nicotine-induced beta cell dysfunction in the beta cell.</p> <p>INS 1E cells, a rat pancreatic beta cell line, were treated with nicotine or vehicle ± 10µM folic acid for 48 hours. Nicotine treatment decreased both basal and glucose stimulated insulin secretion, but had no effect on insulin content, mitochondrial function or markers of apoptosis. Expression of oxidative stress/damage markers (HSP70 and 4-HNE), antioxidant enzymes (Cu/ZnSOD, MnSOD and CAT), insulin gene transcription factor PDX1 and K<sub>ATP </sub>channel subunit kir<sub>6.2</sub> were determined by western blot analysis. Expression of HSP70, 4-HNE and MnSOD were significantly increased with nicotine treatment (p=0.002, 0.05 and 0.03 respectively). Cu/ZnSOD and CAT expression remained unchanged with nicotine treatment. The addition of folic acid significantly reduced HSP70 expression, 4-HNE expression, CAT expression, but did not alter the expression of MnSOD. There was a significant (p6.2expression (p=0.019) which showed a trend toward reduced expression following treatment with folic acid (p=0.067).</p> <p>Nicotine treatment significantly increases markers of oxidative stress and oxidative damage in pancreatic beta cells; an effect which was reversed by folic acid administration. Nicotine and folic acid treatment increased insulin content, likely mediated through an increase in the insulin gene transcription factor, PDX1. Furthermore, nicotine treatment increased expression of kir<sub>6.2, </sub>suggesting a defect in the insulin secretory mechanism. This effect was reversed with folic acid treatment.Although many studies suggest that Canadians are meeting or exceeding recommended folate levels, this is not true in smokers. Our data suggest that additional folate supplementation in smokers may prevent nicotine-induced damage to the pancreas and thus reduce the risk of type 2 diabetes.</p> / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/12875 |
| Date | 04 1900 |
| Creators | Nicholson, Catherine J. |
| Contributors | Holloway, Alison C, Raha, Sandeep, McDonald, Sarah, Medical Sciences (Division of Physiology/Pharmacology) |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | thesis |
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