LA JOLLA, CA Knocking out the gene for a peptide associated with insulin secretion protects mice against the harmful effects of a high-fat diet, report researchers at the Salk Institute for Biological Studies. Their findings, detailed in the Proceedings of the National Academy of Sciences, suggest that urocortin 3, a new peptide recently discovered in the insulin secreting cells of the pancreas, plays a role in the increased production of insulin in response to high caloric intake in animals.
"Many normal mice eventually develop some signs of type 2 diabetes as they age," explains Wylie Vale, Ph.D., who conducted the study in collaboration with Kuo-Fen Lee, Ph.D., both professors in the Clayton Foundation Laboratories for Peptide Biology. "Interestingly, the mutant mice missing the urocortin 3 gene did not develop the age-related insulin resistance and high blood sugar we observed in the normal control mice," adds Vale.
After initial experiments had shown the importance of ucocortin 3 for the secretion of insulin, the Salk researchers bred mice missing the gene for urocortin 3 and compared their metabolism to that of normal mice. When placed on a high caloric diet for three months, the mutant mice packed on the same amount of weight and, as expected, had lower insulin levels. But, to the researchers' surprise, they also had lower blood sugar, improved glucose tolerance curves and didn't develop the fatty livers their unaltered counterparts suffered from.
"It is possible that restraining the abnormally high levels insulin secretion, which occurs with high caloric intake may help to maintain insulin sensitivity and, thus, avoid some of the untoward consequences of the high food intake and weight gain," states first author Chien Li, the postdoctoral researcher who analyzed these mice and has since taken a faculty position at the University of Virginia.