Nutrition researchers track down how soy reduces diabetes risk

Scientists led by Young-Cheul Kim, assistant professor of Nutrition, have identified the molecular pathway that allows foods rich in soy bioactive compounds called isoflavones to lower diabetes and heart disease risk. Eating soy foods has been shown to lower cholesterol, decrease blood glucose levels and improve glucose tolerance in people with diabetes.

According to Kim, the study shows that “what we eat can have tremendous impact on health outcomes by interacting with certain genes. Recent research also suggests that diet can even change the copy number of a certain gene, leading to biological changes.”

Soy is the most common source of isoflavones in food. In experiments with mouse cells, Kim, a molecular nutrition researcher who studies how fat cells develop in the body, and colleagues, focused on daidzein, one of the two main isoflavones found in soy. Many epidemiological observations and human clinical studies have shown that adding soy to one’s diet is associated with lower diabetes risk and improved insulin sensitivity, as well as lower cardiovascular disease risk, Kim notes. However, until now the direct target tissue and molecular pathways by which soy exerts its anti-diabetic effects was not clearly understood.

Kim and colleagues at Southern Illinois University, with others at the universities of Tennessee and Florida, had earlier found that dietary isoflavones reduced the severity of diabetes in an animal model of the disease by increasing the activity of certain transcription regulators in the fat tissue. For the current study, they hypothesized that daidzein and its metabolite, equol, are part of this activation process.

They found that daidzein and equol enhanced adipocyte differentiation, or the formation of fat cells, through activation of a key transcription regulator, the same receptor that mediates the insulin-sensitizing effects of anti-diabetes drugs. Thus, daidzein and equol daidzein and equol seem to work in a similar manner as anti-diabetic drugs currently in the market. Their findings are reported in a September online version of the Journal of Nutritional Biochemistry.

“Our results suggest that soy isoflavones exert anti-diabetic effects by targeting fat cell-specific transcription factors and the downstream signaling molecules that are important for glucose uptake and thus insulin sensitivity,” Kim notes. “The new findings help us to understand the cellular mechanisms.” That is, how these biologically active compounds in soy interact to regulate and initiate metabolic and biological functions.

Results demonstrate that daidzein and equol enhance adipocyte differentiation by activating a specific receptor. The downstream responses include increased expression of three proteins, resulting in enhanced glucose uptake and insulin sensitivity.

“Although some details remain to be worked out, our data provide an additional molecular basis for the mechanism of insulin-sensitizing action by soy isoflavones,” says Kim. “These new findings help fill a critical gap between epidemiological observations and clinical studies on the anti-diabetic benefits of dietary soy.”

Future studies will extend the work to primary cultures of human cells through collaboration with researchers at Pioneer Valley Life Science Institute and Baystate Medical Center in Springfield. If replicated, studies can move on to further work in whole body systems.