(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
