New hormone for lowering blood sugar

April 03, 2012

New evidence points to a hormone that leaves muscles gobbling up sugar as if they can't get enough. That factor, which can be coaxed out of fat stem cells, could lead to a new treatment to lower blood sugar and improve metabolism, according to a report in the April issue of Cell Metabolism, a Cell Press publication.

This new fat-derived hormone would appear to be a useful alternative or add-on to insulin; it can do essentially the same job, sending glucose out of the bloodstream and into muscle.

"It's like you've opened the door and now the glucose can come in," said Jonathan Graff of the University of Texas Southwestern Medical Center.

Graff's team manipulated a key developmental pathway in the fat stem cells of mice to find that the animals showed remarkably low blood sugar levels. The animals' muscles were taking up glucose at two to four times the usual rate thanks to an abundance of glucose transporters at their surfaces. That discovery was all the more striking because the animals also lacked fat stores, a condition known as lipodystrophy that normally results in just the opposite: high blood sugar and diabetes.

The mice could respond normally to insulin, but insulin surprisingly had nothing to do with the muscles' unusual appetite for sugar. The source for the change wasn't anything inherently different in the muscle itself either; it was something about those manipulated fat stem cells.

Further experiments revealed that the mouse muscles continued to take up extra sugar when they were isolated in the lab and exposed to blood serum. "It showed these effects were likely secondary to blood-borne signals sent by the manipulated fat cell progenitors," Graff says.

That signal can be generated only by fat stem cells, not mature fat cells. When the researchers made the same developmental manipulation in adult fat cells, they saw no such effect on blood sugar or muscle.

The findings highlight a new fat to muscle hormonal cue that would seem to have real therapeutic promise.

"If we can purify this factor and give it to people, there is potential for its use to lower and help control blood sugar," Graff says. Alternatively, there might be a way to encourage fat stem cells in the body to produce more of the anti-diabetic factor themselves.
-end-
Zeve et al.: "Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake."

Cell Press

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