Potential Non-Insulin Treatment of Type 1 Diabetes Investigated

Researchers at the University of Texas Southwestern Medical Center have discovered a hormone pathway that potentially could lead to new ways of treating type 1 diabetes independent of insulin, long thought to be the sole regulator of carbohydrates in the liver. Results of this new study are published in the March 25, 2011 issue of Science. Another hormone, fibroblast growth factor 19 (FGF19), has insulin-like characteristics beyond its role in bile acid synthesis. Unlike insulin, however, FGF19 does not cause excess glucose to turn to fat, suggesting that its activation could lead to new treatments for diabetes or obesity. “The fundamental discovery is that there is a pathway that exists that is required for the body, after a meal, to store glucose in the liver and drive protein synthesis. That pathway is independent of insulin,” said Dr. David Mangelsdorf, chairman of pharmacology at UT Southwestern. Naturally elevating this pathway, therefore, could lead to new diabetes treatments outside of insulin therapy. The standard treatment for type 1 diabetes, which affects about 1 million people in the U.S., involves taking insulin multiple times a day to metabolize blood sugar. Dr. Mangelsdorf and Dr. Steven Kliewer, professor of molecular biology and pharmacology at UT Southwestern, are co-senior authors of the study. Dr. Kliewer has been studying the hormone FGF19 since he discovered its involvement in metabolism about eight years ago. Fibroblast growth factors control nutrient metabolism and are released upon bile acid uptake into the small intestine. Bile acids, produced by the liver, break down fats in the body. In this work, researchers studied mice lacking FGF15 – the rodent FGF19 hormone equivalent. These mice, after eating, could not properly maintain blood concentrations of glucose and normal amounts of liver glycogen.
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