The low capability to create new vessels to allow the arrival of nutrients in the cells is the initial cause of the loss of functionality in transplanted pancreatic islets. This analysis is one of the main reasons causing the failure in transplantations in the treatment of type 1 diabetes.
The University of Barcelona researchers and IDIBAPS led a study that identifies a protein as the potential modulator in the revascularization of pancreatic islets. Researchers have conducted a survey on diabetic mice with islet transplant from other animals or human islets and showed that grafts without this protein have higher revascularization, favoring the viability of cells, and normal sugar levels and glucose tolerance are recovered.
Professor at the Faculty of Medicine and Health Sciences of the University of Barcelona, and also head of the IDIBAPS research group Pancreatic Islets, Ramon Gomis, coordinated the study, and researchers at the Diabetes and Associated Metabolic Diseases Networking Biomedical Research Center (CIBERDEM), and Rosa Gasa, researchers in the same group.
Researcher in the IDIBAPS group, Hugo Figueiredo, the first author of the study, published the findings in the journal Science Translational Medicine.
The pancreatic islet transplantation is one of the used strategies in the type 1 diabetes treatment, based on regenerative medicine. They have their formation through different types of cells with an endocrine function that produces hormones such as insulin and glucagon. In type 1 diabetes, beta cells in islets, responsible for the production of insulin, are selectively destroyed by an autoimmune process.
As a result of this, islet transplantation can restore the physiological function in patients with this type of diabetes. The coordinator of the study, Ramon Gomis, said that although some centers carry out this transplant, it has limitations, including the chronic administration of immunosuppressants, and it is applied in those cases in which the disease is not adequately controlled. Right now, it is indicated in the context of a kidney transplant, and they opt for a dual vascular kidney, pancreas transplant.
The team discovered, in their research, a molecular target called PTP1B phosphatize, which would allow transplanted pancreatic islets to be viable. The outcomes reveal the inhibition of this enzyme, present in all cells, including pancreatic beta cells, promotes the activity of the pro-angiogenic growth factor VEGF, which enables the creation of new blood vessels. It gives a higher re-vascularization of the treatment, therefore, that improves the islet survival and functionality. Rosa Gasa noted that hypoxia-induced the regulation of the re-vascularization the lack of nutrients and the inhibition of phosphatizing widens this response. The creation of new blood vessels stops when the stimuli disappear.
Ramon Gomis concluded that this article is a concept proof that can remove one of the reasons why the pancreatic islet transplant fails. There are less specific inhibitors of PTP1B and phosphatizes, and therefore, the next step will be to test these inhibitors in the islet transplant in humans and assess its success.
