Potential Non-Insulin Type 1 Diabetes Treatment Discovered

(National Institutes of Health

Researchers at University of Texas Southwestern Medical Center in Dallas and three other institutions have discovered a hormone pathway that could lead to new ways of treating type 1 diabetes. Results of this study appear in the March 25 issue of the journal Science (paid subscription required).

Type 1 diabetes is usually diagnosed in children and young adults, according to the American Diabetes Association. In type 1 diabetes, the body does not produce insulin, a hormone that is needed to convert sugar, starches and other food into energy needed for daily life. About 1 in every 400 to 600 children and adolescents has type 1 diabetes .

Insulin has long been considered the sole regulator of carbohydrates in the liver. Researchers led by Southwestern pharmacologists David Mangelsdorf and Steven Kliewer have found another hormone —  fibroblast growth factor 19 (FGF19) — that has insulin-like properties beyond its role in bile acid synthesis.

Insulin therapy is the standard treatment for type 1 diabetes and involves taking insulin multiple times a day to metabolize blood sugar. Unlike insulin, however, FGF19 does not cause excess glucose to turn to fat. This property indicates that activating FGF19 could lead to new treatments for diabetes or obesity.

Fibroblast growth factors control the metabolism of nutrients and are released upon bile acid uptake into the small intestine. Bile acids, produced by the liver, break down fats in the body.

The research team studied mice lacking the rodent equivalent of FGF19, which after eating, could not properly maintain blood concentrations of glucose and normal amounts of liver glycogen. Glycogen is a form of glucose storage found mainly in liver and muscle tissue.

The mice were then injected with FGF19 to evaluate its effects on metabolism in the liver. FGF19 restored glycogen levels in the mice lacking the rodent equivalent hormone. When given to diabetic mice lacking insulin, FGF19 also corrected the loss of glycogen.

As an alternative to insulin therapy, however, FGF19 first needs to address serious side effects. In some studies, says Mangelsdorf, activating the hormone in rodents caused the liver to grow and develop cancer.

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