Know-how of scientists from Salk

Personalized Beta Cells Respond to Glucose

LifeSciencesToday based on Salk News: Salk scientists find “secret sauce" for personalized, functional insulin-producing cells

From the patient's cells, scientists from the Salk Institute created beta cells of the pancreas capable of responding to glucagon (red) and producing insulin (green). These cells can be transplanted into the patient's body for the treatment of diabetes.
(Photo: Salk Institute)

Scientists from the Salk Institute for Biological Studies have solved a long–standing problem - they have obtained functional cells for the treatment of patients suffering from diabetes. They discovered an energy "switch", the "activation" of which in the cells of the pancreas enhances their reaction to glucose – a stage that no research group has been able to pass. The result of their work is hundreds of millions of human beta cells obtained in the laboratory, which cure mice from diabetes. An article about the study (Yoshihara et al., Error Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells) is published in the journal Cell Metabolism.

For more than a decade, scientists around the world have been trying to create a replacement for pancreatic cells that have lost the ability to perform their function, which is the cause of juvenile autoimmune diabetes (type 1 diabetes) and obesity-related adult diabetes (type 2 diabetes). Although cells grown in the laboratory are capable of producing insulin, they do not respond – or respond insufficiently –to glucose.

 "We have found a previously unknown energy switch needed to produce healthy functional human beta cells, which makes this discovery the basis for a promising method of treating human diabetes," says Ronald Evans, director of the Salk Institute Gene Expression Laboratory, co-director of the study.

The method developed at the Salk Institute begins with induced pluripotent stem cells, a cellular technology in which tissue cells – for example, skin cells – of a patient are reprogrammed into cells of other types, in particular, into pancreatic cells. This stage makes it possible to obtain pre-beta cells that are not yet functional, although they produce insulin, and several research groups have successfully passed it. But the path to functional beta cells remained unknown.

"To work effectively, pancreatic cells must be able to do two things: react to glucose and produce insulin," explains Professor Evans. "Until today, no one has been able to find a way to get pancreatic cells from patient cells that can do both."

The researchers studied in detail the fundamental biology of the beta cell and discovered several transcription factors that were turned off, but could keep under their control the transition of the cell to a fully functional state.

The know-how of Professor Evans and his colleagues is based on one of these factors, the role of which in cellular signaling has been studied by researchers for many years. This protein – ERR-gamma – is crucial for awakening "silent" beta cells – endowing them with the ability to respond to glucose and, accordingly, release insulin.

Figure from an article in Cell Metabolism – VM.

"This achievement results in a more controlled insulin response than the methods currently available," says study co–leader Michael Downes, a senior researcher at the Salk Institute. "Nothing was known about the maturation process of beta cells. We looked into this black box, and now we know what's going on there."

The technology developed by the group is a simple, fast and inexpensive way to obtain human pancreatic beta cells suitable for transplantation in the laboratory that are genetically compatible with the patient, the scientist adds.

"By adding ERR-gamma to pre-diabetic beta cells in a Petri dish, we have successfully obtained glucose-responsive cells close to beta cells," comments Eiji Yoshihara, the first author of the article, on the results of the experiments. "The removal of ERR-gamma in animals cancels the reaction to glucose, proving that this factor is the main regulator of beta cell maturation."

But is it possible to successfully treat diabetes with these beta cells? Professor Evans and his colleagues found that transplantation of mature beta cells obtained by this method to mice with a type 1 diabetes model quickly cured the animals of the disease.

"Let's hope that this reflects what will happen in the clinic – a patient diagnosed with diabetes can potentially be treated with this method," Evans sums up. "This is very interesting because it shows that the cells obtained in the laboratory are ready for use."

The researchers hope to start clinical trials on patients in the next few years. 

Portal "Eternal youth" http://vechnayamolodost.ru  15.04.2016