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Molecular and cellular determinants of the function, damage and protection of pancreatic islets Regenerative medicine and advanced therapies
Coordinator: Franz Martín Bermudo
1 Function and regulation of pancreatic islets: molecular and cellular bases and
therapeutic targets
It has been shown that the rescue of natural TRF1 reduction with age by means of gene therapy improves the glucose intolerance associated with ageing (Dereveyanko et al , Aging Cell 2017)
In the Ngn3 gene an amplifying region has been identi ed which corrects its expression in pancreatic progenitor cells “Cis” elements have been seen in this which are recruited for this function (Van Arens- bergen et al , PloS One 2017)
Islets de cient in GATA6 activity have an altered secretion of insulin, a lower content in the hormone, im- mature insulin granules, a disorganised endoplasmic reticulum and swollen mitochondria In adult beta cells the loss of GATA6 a ects the expression of genes which are vital for their functioning (Villamayor et al , Diabetes 2017)
In pro-opiomelanocortin (POMC) neurons, it has been described that the protein of mitochondrial mem- brane Mitofusin 1 is able to couple the detection of the circulating levels of nutrients with the metabolism of glucose Its alteration also a ects the homeostasis of glucose (Ramírez et al , Cell Metab 2017)
At low concentrations of glucose, the pancreatic islets increase the expression of miR-708 Their potential target is probably the Neuronatin protein (Nnat) The increase in the expression of miR- 708 alters glu- cose-stimulated insulin secretion (GSIS), which recovers after over-expressing Nnat miR-708 inhibition recovers the damage in GSIS produced by the low concentrations of glucose The over-expression of miR-708 suppresses the proliferation of beta cells and induces their apoptosis (Rodriguez-Comas et al , Diabetes 2017)
An ALX3 de cit increases the risk of congenital malformations associated with gestational diabetes (García-Sanz et al , Sci Rep 2017)
58 CIBER ANNUAL REPORT 2017
