New data on how insulin-like hormone works reinforces its potential as diabetes treatment

By Debbie Bolles / September 2011

The recent discovery by UT Southwestern researchers that a hormone with insulin-like characteristics blocks the liver’s production of glucose could one day lead to new drugs to treat type 2 diabetes.

In an earlier finding published in Science, the same research team learned that this hormone, fibroblast growth factor 19 (FGF19), stores glucose in the liver and drives protein synthesis similar to but independent from insulin. The newest data on how FGF19 works, published recently in Cell Metabolism, provides evidence that regulating this hormone pathway could help those with any type of diabetes.

Dr. Steven Kliewer
Dr. Steven Kliewer

“This hormone has been shown to improve glucose levels in diabetic animals. It stomps out glucose production, but doesn’t cause the production of fat,” said Dr. Steven Kliewer, professor of molecular biology and pharmacology.

Dr. Kliewer, co-senior author of these related studies with Dr. David Mangelsdorf, chairman of pharmacology, said FGF19 has a unique ability to keep glucose production in check hours after insulin’s similar job has faded. What’s more, this hormone doesn’t cause fat to be stored as insulin does.

Although this mouse model study is a long way from development of a drug to treat diabetes, the finding is significant because more than 90 percent of diabetics have the insulin-resistant type 2 variety. For the estimated 20 million Americans with this disease, their bodies do not make enough insulin to process glucose into energy effectively. Drugs to control high blood glucose levels vary, and may include insulin.

“This highlights the importance of coming up with new ways of regulating these pathways that do not rely on insulin,” Dr. Kliewer said.

Dr. Kliewer has been studying FGF19 for about eight years. The hormone controls nutrient metabolism and is released upon bile acid uptake into the small intestine. Bile acids, produced by the liver, break down fats in the body.

“The Cell Metabolism paper is the second of a one-two punch showing that an important additional function of FGF19 is its ability to turn off hepatic glucose production,” said Dr. Mangelsdorf, a Howard Hughes Medical Institute (HHMI) investigator at the medical center.

Other UT Southwestern researchers involved in the study were Dr. Matthew Potthoff, lead author and a postdoctoral research fellow in pharmacology; Jamie Boney-Montoya, research assistant in molecular biology, Dr. Robert Gerard, associate professor of internal medicine and molecular biology; Dr. Mihwa Choi, a former postdoctoral fellow in molecular biology; and from the Advanced Imaging Research Center, Dr. Shawn Burgess, assistant professor; Tianteng He, senior research associate; Dr. Nishanth Sunny, assistant instructor; and Dr. Santhosh Satapati, postdoctoral researcher. Also involved in the study were researchers from Van Andel Research Institute and Washington University School of Medicine.

The work was supported by the National Institutes of Health, HHMI and the Robert Welch Foundation.

Dr. Kliewer holds the Nancy B. and Jake L. Hamon Distinguished Chair in Basic Cancer Research.
Dr. Mangelsdorf holds the Beatrice and Miguel Elias Distinguished Chair in Biomedical Science and the Distinguished Chair in Pharmacology.