Metabolic Disease: Understanding How The Brain Can Influence The Effects Of Insulin

New data, generated in rats, by Hiraku Ono and colleagues, at Albert Einstein College of Medicine, New York, has provided insight into a molecular pathway in the hypothalamus that contributes to the development of insulin resistance.

Insulin plays a key role in controlling the amount of glucose in the body through its ability to make cells, such as liver and fat cells, take up glucose from the blood and store it for future use. Insulin also prevents liver cells from releasing stored glucose, partly through its effects in the hypothalamus. In the study, if rats were fed a high-fat diet for a short period of time the ability of insulin to prevent liver cells releasing stored glucose was reduced. This was associated with both a decrease in insulin-induced signaling and an increase in activation of a protein known as SK6 in the hypothalamus.

The importance of SK6 activation in the hypothalamus in suppressing the ability of insulin to prevent glucose release from liver cells was confirmed by two sets of experiments. First, it was shown that enforced SK6 activation in the hypothalamus had the same effects as feeding rats a high-fat diet; second, blocking the effects of SK6 activation restored the ability of insulin to prevent glucose release from liver cells, even when rats were fed a high-fat diet. These data lead the authors to speculate that the earliest stages of diet-induced insulin resistance might be prevented by inhibition of S6K in the hypothalamus.