Gene Reverses Diabetes?
Reported January 11, 2010
(Ivanhoe Newswire) — Even a very small amount of the fat hormone leptin goes a long way when it comes to correcting diabetes. The hormone controls the activity of a gene in the liver, which has anti-diabetic effects in animals and could have similar therapeutic effect in humans.
The new findings confirm what some at least had already suspected, that leptin’s anti-diabetic effects are independent of the hormone’s well-known ability to reduce body weight.
“It was surprising to me how potent leptin was in treating diabetes,” Jeffrey Friedman of Rockefeller University was quoted as saying. “It had a highly significant impact at plasma levels that were undetectable.”
Leptin’s usefulness as a therapy has been demonstrated in people with rare metabolic disorders. Studies that sought to address how the hormone, which is produced in fat tissue, acts to improve diabetes were complicated by the fact that leptin also causes marked weight loss, which by itself can improve diabetes.
To get around that issue in the new study, Friedman and colleagues first identified the lowest dose of leptin that could correct insulin resistance and diabetes without leading animals to eat less or to lose weight. They then looked to see how the very low-level infusion of leptin changed the activity of genes in the animals’ livers. That survey led them to the gene known as IGFBP2.
Treatments designed to increase IGFBP2 expression in obese and diabetic mice reversed their diabetes. Further study showed that animals treated with the protein responded to insulin three times better than untreated ones.
Researchers also found that leptin-deficient patients do indeed have lower blood levels of IGFBP2 at baseline and that those levels can be raised with low-dose leptin treatment.
“In summary,” the researchers concluded, “we have developed a set of conditions in which leptin treatment potently improves diabetes independent of its ability to correct weight and food intake. This protocol was used to identify IGFBP2 as a leptin-regulated gene whose expression is correlated with leptin’s anti-diabetic effect.”
SOURCE: Cell Metabolism, January, 2010