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Molecular mechanisms associated with the appearance and progression of chronic complications of diabetes: therapeutic strategies
In this line of research, a proteomic analysis on human retina has been made, explaining common pathways of neurodegeneration of the retina and brain (Sundstrom et al., Invest Ophthalmol Vis Sci 2018).
Gene therapy was successfully tried out with whole protein SOCS1 and the mimetic peptide
Molecular and Cellular determinants of the Function, Lesion and Protection of Pancreatic Islets. Regenerative Medicine and Advanced therapies
Coordinator:
Franz Martín Bermudo
Function and regulation of pancreatic islets: molecular and cellular bases and therapeutic targets
The chemical modulation of repressor mark H3K27me3 has been shown to allow modification of in vitro Neurogenin 3-mediated gene activation. This opens up options for generation of protocols for obtaining insulin-producing cells (Fontcuberta-PiSunyer et al., BBA-Gene Regul Mech 2018).
Another of the accomplishments worthy of mention is that it has been described that specific inactivation of GATA6 in the pancreatic islets of mice reduces their insulin content, alters insulin secretion, generates ultra-structural alterations and affects the expression of specific genes of the beta cell. The animals also undergo an alteration of glycaemia homeostasis, indicating the importance of GATA6 in the function of pancreatic beta cells (Villamayor et al., Diabetes 2018).
in renal and vascular complications of diabetes in murine models (López-Sanz et al., Lab Invest 2018).
We should lastly highlight the fact that a dual role of protein tyrosine phosphatase 1B has been discovered in non-alcoholic steatohepatitis due to the modulation of pro-inflammatory pathways in immune cells of the liver during its progression and modulation of the pathways for signalling
the proliferation of oval liver cells during its reversion (González-Rodríguez et al., Molecular Metabolism 2018).
Preventive and therapeutic strategies in regenerative medicine, cell therapy and gene therapy
We have managed to develop a new model for experimental transplants of human islets to immunodeficient mice which enables reducing the number of islets and animals necessary for the transplant, increases animal comfort and optimises resources by reducing the workload of researchers and carers (Estil·les et al., Cell Transplant 2018).
It has also been possible to report the capacity of gene therapy with FGF21 to treat diabetes and its associated metabolic diseases. The use of adeno- associated viral vectors to genetically modify the liver, adipose tissue or the muscle so that they secrete FGF21 blocks the appearance of resistance to insulin and obesity in ob/ob mice, fed for long periods of time with high-fat diets. (Jimenez et al, EMBO Molecular Medicine 2018).
It has been described how microRNA miR-7 is expressed in a different way during the process of differentiating human embryo stem cells (hESCs) towards insulin-producing cells and that their modulation plays an important role in the appearance of beta pancreatic cells. This finding can be exploited to optimise differentiation protocols of hESCs towards insulin-producing cells (Lopez-Beas et al., Mol Ther Nucleic Acids 2018).
Application of new technologies to treatment of diabetes
Current artificial pancreas systems are mainly hybrid systems which require a statement of intake.
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CIBERDEM | ANNUAL REPORT 2018