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Do rodents hold the secret to curing diabetes?

In rodents with type 2 diabetes, a single surgical injection of a protein called fibroblast growth factor 1 can restore blood sugar levels to normal for weeks or months. Yet how this growth factor acts in the brain to generate this lasting benefit has been poorly understood.

Clarifying how this occurs might lead to more effective diabetes treatments that tap into the brain's inherent potential to ameliorate the condition.

"Until recently, the brain's ability to normalize elevated blood sugar levels in diabetic animals was unrecognized," said Dr. Michael Schwartz, professor of medicine at the University of Washington School of Medicine and co-director of the UW Medicine Diabetes Institute. "By interrogating cellular and molecular responses induced in the hypothalamus by a brain peptide called fibroblast growth factor 1, our international teams' latest findings chart a path towards a more complete understanding of how this effect is achieved.

"These insights," he said, "may one day inform therapeutic strategies for inducing sustained diabetes remission, rather than simply lowering blood sugar levels on a day-to-day basis as current treatments do."

Type 2 diabetes affects 10% of the U.S. population. It is closely tied to obesity and causes serious health problems including heart disease, vision loss, kidney failure, dementia, difficult-to-cure infections, and nerve damage. It also increases the risk of needing amputations. Control of blood sugar levels can prevent these problems but is often hard to achieve and becomes an ongoing struggle for many patients.

In two companion papers in the Sept. 7 editions of Nature Communications and Nature Metabolism, international teams of researchers describe the intricate biology of the brain's response to fibroblast growth factor 1. The first team describes robust cellular responses that appear to safeguard brain-signaling pathways critical to keeping blood sugar in check.

A second team, containing some of the same researchers, made discoveries about extracellular matrix assemblies called "perineuronal nets" that enmesh groups of neurons involved in blood sugar control. The investigators learned that fibroblast growth factor 1 repairs perineuronal nets that have been damaged by diabetes. This response is required for diabetes remission to be sustained.

Dr. Tunes Pers, of the Novo Nordisk Foundation Center for Basic Metabolic Research, the University of Copenhagen in Denmark, and diabetes and obesity researcher Dr. Michael Schwartz at UW Medicine in Seattle were senior authors of the Nature Communications report. The lead authors from their labs were Dr. Marie Bentsen and Dr. Dylan Rausch.