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Leptin: Could It Be The Connection Between Obesity and Diabetes?

The word leptin comes from the Greek word leptos, meaning thin. A hormone produced by fat cells, it binds to a spot in the brain known as the satiety center, thereby announcing to the brain that the body has had enough to eat, that plenty of energy is stored in the fat, and that there is no need to eat any more right now. In short, its effect on the brain is to reduce appetite.

Obese people have a lot of stored fat, and they produce unusually high levels of leptin. Unfortunately, their leptin doesn’t work like it’s supposed to. Why that occurs was the subject of recent research about leptin’s effects on beta cells, performed by scientists at the Joslin Center. Previous test tube studies have found leptin receptors in the pancreas as well as the brain. When leptin binds to the pancreas receptors, it inhibits insulin secretion in the beta cells; that is, it keeps insulin levels from getting too high.

To figure out why that mechanism fails to work in obese people, the researchers engineered themselves some mice that lacked leptin receptors in the pancreas. Those mice showed improved glucose tolerance, greater insulin secretion, and beta cell growth. Since leptin keeps insulin levels from getting too high, the lack of leptin action apparently enhanced beta cell functioning and promoted insulin secretion.

Then the researchers put those engineered mice and some control mice on a high fat diet. Both groups of mice grew obese, but, oddly enough, the mice without the leptin receptors developed glucose intolerance and insulin resistance, both of which are way stations on the road to diabetes.

The researchers speculate that leptin resistance in pancreatic beta cells somehow contributes to high insulin levels, beta cell failure, and the consequent glucose intolerance experienced by obese people. Future studies will look at the interaction of insulin and leptin signaling in beta cells in an effort to further explain the relationship between diabetes and obesity.

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Sources: Joslin Diabetes Center, October 2007; Wikipedia; Journal of Clinical Investigation, September 2007

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