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Insulin: In Need of Some Restraint?

Wylie Vale and Kuo-Fen Lee, professors in the Clayton Foundation Laboratories for Peptide Biology, have reported in Proceedings of the National Academy of Sciences that loss of a gene encoding a peptide promoting insulin secretion protects mice against harmful effects of a high-fat diet. Vale and postdoctoral fellow Chien Li had shown that the peptide, urocortin-3, which is expressed in pancreatic islet cells, promotes increased insulin secretion following high caloric intake.

So the researchers deleted, or "knocked out," urocortin-3 in genes of a mouse and analyzed metabolism of knock-out mice. When fed a high calorie diet, urocortin-3 knock-out and normal mice gained equivalent weight and showed lower insulin levels. But knock-out mice showed lower blood sugar and improved glucose tolerance curves, and didn't develop fatty livers seen in normal mice under that diet.

The Vale and Lee labs with postdoctoral fellow Alon Chen had shown that the closely related gene, urocortin-2, acts within muscle to regulate insulin sensitivity of that tissue. They hypothesize that the two urocortins act in concert to modulate insulin secretion and sensitivity. They will now determine whether urocortins have additive effects by examining mice in which both urocortin genes are knocked out. These studies may provide a rationale for developing therapeutic means of suppressing or blocking the actions of both peptides for the management of type 2 diabetes.