Group of redox biology
Violation of the secretion of insulin is the main cause of diabetes. It is well known that the secretion of insulin by the pancreas is regulated by intracellular signaling of the beta cells of the islets of Langerhans, and active forms of oxygen (ROS) are directly involved in this process.
Today, there is no clear idea of the mechanism of action of ROS in the regulation of insulin secretion, and the data obtained in vivo and in vitro vary greatly, which is due to the lack of endogenous products of ROS without activation of different upstream proteins of the signal cascades. Using the yeast oxidase D-amino acids (DAO), we can specifically regulate the production of ROS in various compartments of beta cells, and answer the question of the effect of local concentrations of ROS in beta cells on insulin production in vitro (primary and immortalized beta cell cultures) and in animals in vivo.
The use of DAO allows stimulating the production of ROS non-invasively by simply introducing into the cellular medium or drinking water of the animal D-amino acids, which are substrates of this oxidase. D-aminoacids easily penetrate into various cellular compartments and organs. Monitoring the level of glucose and insulin in the blood of an animal using ELISA allows long time observation of changes in the metabolic state of the animal by blood analysis.
In combination with the latest genetically encoded probes allowing monitoring of calcium fluctuations (GCaMP6s), hydrogen peroxide (HyPer1-3, HyPerRed), insulin granules (RINS1) and local expression of DAO, we can multiparametrically observe the production of hydrogen peroxide and insulin secretion signal processes.
Monitoring of the level of expression of the cells redox-response genes, as well as genes markers of the development of pathological states of beta cells, will allow comparing the effect of oxidative stress on beta cells with the processes occurring during the development of diseases.
During the project implementation, in vitro and in vivo data on the effect of ROS on the insulin secretion by pancreatic cells will be obtained, and it will also be established whether excessive production of ROS can lead to the development of type 1 or 2 diabetes or insulin resistance.
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