Scott Brunson and Professor Chad Hancock, Department of Nutrition, Dietetics, and Food Science

Background

Due to dramatic increases in type II diabetes, studies on insulin resistance are especially applicable to this current health issue. Previous epidemiological studies examining selenium’s effect on prostate cancer observed a possible correlation between increased risk for type II diabetes mellitus and increased selenium levels in humans (Lippman, S.M.2009). However, in other studies contradictory results have been recorded. Due to these inconsistencies we are investigating the effects of selenium on insulin resistance. If increased dietary selenium causes insulin resistance, we will examine the mechanism by which this occurs.

Selenium is a micronutrient that plays a critical role in maintenance and regulation of energy metabolism. It is also involved in maintaining normal antioxidant status. We have collected preliminary data on mice which indicate that a diet with the addition of supplemental selenium increases central adiposity. This is a sign that selenium could be increasing insulin resistance. Because prior research has focused on the potential for selenium to prevent cancer, it is very important to understand potential disadvantages of selenium supplementation. Therefore, the purpose of this experiment is to determine whether an increase in selenium through dietary supplementation will cause skeletal muscle insulin resistance.

Results

Preliminary data has been collected from male offspring of fvb mice crossed with bI6 mice. These mice are given food ad libitum. They received a standard chow diet (Harlan 8604) or a diet with decreased isoflavones. Next half of those animals had Se-methyselenocystein supplements mixed within their chow. This is a naturally occurring food form of the mineral. At the time of sacrifice the epididymal, retroperitoneal, and mesenteric fat pats are removed, weighed, and frozen in liquid nitrogen.

(Figure 1) Shows recorded abdominal fat from mice in four treatment groups. Isoflavone caused a decrease in fat. Selenium was found to negate some of isoflavone’s effect. However, Selenium alone caused its own decrease in abdominal fat from the control group.

Following the data collected from mice we started a new study using male wistar rats. We created two new diets that are more identically matched in content with the exception of one having increased isoflavone content over the other. In order to increase control of selenium supplementation we daily orally administered 1 mg Se/kg of Se-methyselenocysteine. During the 69 days of treatment bodyweight was measured daily. We found no significant difference in body weight between diets.

Beginning the second week of treatment we recorded two-day feed consumption. Prior research has found that certain forms of selenium cause decrease feed consumption (Mueller, A.S. 2004). Another study found that isoflavones cause rats to increase feed consumptions (Lephart, E.D. 2004). During the first six measurements we found no difference of feed consumption between treatments. However, on our last measure of feed consumption we found increased consumption among animals receiving high isoflavones.

(Figure 2) Feed consumption data from rats in four treatment groups. Those receiving a treatment of higher isoflavones were consuming 3.75 grams or 11.6 kcal more per day.

Using Dual-Energy X-Ray Absorptiometry (DEXA) scans we monitored body composition of the animals. No significant differences abdominal adipose tissue was found between treatment groups. This was further confirmed by dissecting and weighing out the abdominal adipose tissue of the animals. However, more analysis of the DEXA scans is required to determine significance of a trend in the rate of adipose tissue accumulation.

Ongoing Research

This study is ongoing. We will measure protein content of muscles using western blot analysis. Using these muscles we will measure levels of various proteins; i.e., Actin, AMPK, COXI, GLUT4. Using blood samples we will determine selenium’s effect on glutathione peroxidase. Brown adipose tissue was collected from all the animals in order to measure UCP-1 protein content. Using liver samples we will compare treatment effects on liver triglyceride levels. Prostates were collected in collaboration with research on prostate cancer.

References

• Lippman, S.M. (2009) Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers. JAMA 301(1):39-51
• Mueller, A.S. (2004) Effects of a supranutritional dose of selenate compared with selenite on insulin sensitivity in type II diabetic dbdb mice. J. Anim. Physiol. Anim. Nutr. 89:94-104.
• Lephart, E.D. (2004) Dietary isoflavones alter regulatory behaviors, metabolic hormones and neuroendocrine function in Long-Evans male rats. Nutrition & Metabolism 1:16