The loss of the identity of beta cells, a process also called defiffeference of beta cells, is one of the main reasons for the development of diabetes
The interactive doctor
February 24, 2020. 1:59 pm
Investigators at Helmholtz Zentrum München (Germany) have demonstrated for the first time in an experimental model that a combination of directed drugs is capable of restoring the function of beta cells, achieving their redifferentiation and, therefore, potentially opening new roads for remissionof diabetes.
It has been proposed that the loss of the identity of beta cells that secrete insulin in the Islet of Langerhans, a process also called defiffeference of beta cells, is one of the main reasons for the development of diabetes.It is unknown if defiffened beta cells can be the objective of a pharmacological intervention for the regeneration of beta cells and how it can be done.
Under certain conditions, beta cells can lose their identity and retreat to a less differentiated state in which they lose most of their previous functions.It has been proposed that this disdain contributes to a continuous degenerative process of beta cell dysfunction.Current pharmacological treatments for diabetes are not able to stop the decline of mass loss of functional beta cells.The sooner this decline can be prevented, ideally and when the first symptoms of diabetes appear, the greater the amount and level of function of the beta cells that will be kept.
To investigate whether disdainful beta cells can be directed with a combination of drugs to restore the function of beta cells, the researchers used diabetes induced by eighteen in an experimental model.Straptozotocin kills beta cells of insulin producers and severe diabetes cause.However, when injected into multiple low doses, some beta cells survive, which replicates the decrease in the function that researchers wanted to establish for their experiment.
Using unicellular RNA sequencing, researchers could demonstrate that after streptozotocin treatment, surviving beta cells are blurred in a dysfunctional state.The simplicity of the model used (without genetic lesions or autoimmunity) would help them better control the effect of pharmacological treatment.
The team then tested the combination of drugs due to its potential to restore the function of beta cells.To do this, they stratified seven diabetic mice cohorts and treated them daily for 100 days with unique and combinatorial pharmacology.The researchers showed that a stable peptide similar to glucagon-1 (LPG-1)/estrogen conjugate, allows the selective and directed delivery of the load of nuclear hormones to beta cells.
The combination of LPG-1/estrogen and a prolonged action insulin was superior to mono-treatment to normalize glycemia, glucose tolerance, to increase pancreatic insulin content and to increase the number of beta cells.The administration of high doses of LPG-1/estrogen showed signs of systemic toxicity in the study model, a previous requirement for any future clinical test.
Researchers could also demonstrate that LPG-1/estrogen, but not LPG-1 or estrogen alone, increases the function of human beta cells when human pancreatic islets are exposed to the stress of cytokines, which is known to harmThe function of beta cellshuman
"Our study not only describes the paths and processes of the disdain of beta cells, but also demonstrates the potential of simple and combined pharmacological treatments to achieve the remission of diabetes when addressing the flavored beta cells," explains another of theAuthors, Heiko Lickert.
