A new way to develop diabetes therapy

Rodents were cured of diabetes by a single injection into the brain

Oleg Lischuk, N+1

American scientists have managed to achieve stable normalization of glucose levels in mice and rats with diabetes by a single injection of a signaling molecule into the brain. The results of the work are published in the journal Nature Medicine (Scarlett et al., Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents).

The staff of the University of Washington in Seattle with colleagues from other scientific centers of the country decided to use fibroblast growth factor type 1 (FGF1), since it binds to all known types of FGF receptors without requiring coreceptors (in previous works, FGF19 and FGF21 were used, which do not act on all receptors and need the β-Klotho coreceptor; their subcutaneous injection led to normalization of glucose levels for several days). Mice and rats with genetically programmed leptin deficiency were used as a model of type 2 diabetes mellitus.

Three micrograms of FGF1 were injected once into the lateral ventricle of the animal brain, which is ten times less than necessary for hypoglycemic effect with subcutaneous injection (this route of administration provided an effect for 42 hours). After six hours, the level of glucose in the blood of the animals decreased by a quarter. Further observation of animals that were restricted in food and ate their fill showed that a week after the injection, the sugar level completely returned to normal. This effect persisted for 17 weeks, after which monitoring was discontinued, considering that a stable remission had been achieved. No changes in sugar levels were observed in healthy animals after FGF1 injection.

The decrease in glucose levels in animals was not associated with changes in the production of insulin and glucagon (pancreatic hormones regulating sugar metabolism), but required sufficient basal insulin secretion. Subsequent experiments showed that this effect also did not depend on the amount of food consumed and body weight, as well as on the activity of the hypothalamic-pituitary-adrenal system (that is, the production of the hormone cortisol, which increases glucose levels). The results obtained could be reproduced on any other models of diabetes in animals, which means that glucose control was not associated with leptin metabolism.

Scientists have found that the central action of FGF1 stimulates the capture and utilization of glucose by the liver and skeletal muscles, but not by other tissues, and this effect is not associated with modulating the action of insulin and glucagon. The mechanism of such regulation has yet to be clarified, but researchers suggest that it is associated with the restructuring of neuronal connections that regulate the metabolic activity of peripheral tissues. This is supported by an increase in the expression of the transcription factor c-Fos in tanycytes and an increase in the density of synaptic connections in the hypothalamus, which were observed in animals after FGF1 injection.

Tanicytes are specialized cells lining the bottom of the third ventricle of the brain and involved in the metabolism between the bloodstream and cerebrospinal fluid – VM.

FGF1 itself is unlikely to be used as a treatment for diabetes, as it stimulates cell division and can have a carcinogenic effect. However, the discovery of a previously unknown central mechanism for regulating glucose levels opens the way to the creation of fundamentally new effective hypoglycemic drugs.

"From a more general point of view, our study showed that the brain is able to provide a long–term reduction in glucose levels," explained lead author Jared Scarlett (Jarrad Scarlett).

FGF1 is a representative of the fibroblast growth factor family, which provide cell division and life cycle. They play an important role in embryonic development, morphogenesis, organogenesis, tissue repair, vascular growth, as well as the growth and spread of tumors.

Portal "Eternal youth" http://vechnayamolodost.ru  26.05.2016