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Insulin -- in need of some restraint?

the kind that results from over eating and obesity. "Insulin is very effective at lowering blood sugar, and promotes fat storage, preparing the animal for times when food may not be available," he says. "But when the hormone is produced at too high a level for too long, the body becomes insulin resistant and blood sugar and certain blood lipids gradually creep up, which can cause progressive damage to multiple organs."

Urocortin 3 is the second urocortin peptide that this laboratory has found to restrain insulin production or action. In a study published last October in Proceedings of the National Academy of Sciences, Vale, Lee and Alon Chen, Ph.D., a former postdoctoral researcher in Vale's laboratory, who is now at the Weizmann Institute of Science in Israel and Gerald Schuman, M.D., Yale School of Medicine, described a physiological function of urocortin 2.

They found that this peptide is highly produced in skeletal muscle, and functions as a negative regulator of insulin action and glucose use in those tissues. Mice lacking urocortin 2 had increased insulin sensitivity, and were protected against high calorie induced-insulin resistance over time just like mice without urocortin 3. Additionally, the urocortin 2-deficient mice had less body fat and greater lean body mass.

Vale, Lee and their collaborators are now piecing together a global view of how these urocortin peptides, which are members of the corticotropin-releasing factor family, and their receptors regulate responses to physical and even psychological stimuli. The Salk group has been involved in the discovery of all of these peptide hormones as well as their receptors.

Urocortin 2 and urocortin 3 are part of the system that allows the body to secrete and respond to insulin as appropriate, Vale says. "We have found both ligands and their receptor that play important roles in insulin secretion and sensitivity. But they are not the only regulators in this very comp
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Contact: Gina Kirchweger
Kirchweger@salk.edu
858-453-4100 x1340
Salk Institute
6-Mar-2007


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