Page 17 - CIBERDEM2016-ENG

PROGRAMME 2. Molecular and cellular determinants of the function, damage and protection of pancreatic islets. Regenerative medicine and advanced therapies
Coordinator: : Francisco Martín Bermudo
FUnCTIOn AnD REgULATIOn OF PAnCREATIC ISLETS: MOLECULAR AnD
CELLULAR BASES AnD THERAPEUTIC TARgETS.
Different mechanisms increasing defence and improving the function and survival of β cells have been studied, such as the overexpression of endogenous chaperone PDI (Montane et al., Mol Cell Endocrinol 2016), the inhibition of microRnA-708; the use of gLP-1 (Fernández-Millán et al., Free Radic Biol Med 2016) and the reduction in the local expression of Igf-2.
As part of the function and adaptation of β cells a description was given of how a reduction in the expansion capacity of β mass is induced during ageing, caused by a limitation in its neogenesis and by
a dedifferentiation of the β cell. At the same time the capacity for β cell hypertrophy and hyperplasia is maintained (Tellez et al., Am J Physiol Endoc Metab 2016). We have also characterised the mechanism used by TUDCA bile acid in the regulation of the function of β cells and we have generated a new animal model for in vivo study in real time of the role of IRS2 in β cells (Vettorazzi et al., Metabolism 2016).
The study of the molecular and cellular bases of the function and regulation of pancreatic islets has enabled us to find out that some lncRNAs display altered regulation of type 2 diabetes, showing a new type of molecular target (Akerman et al., Cell Metab 2017), that Wnt9a acts as a target gene of ngn3 and that the loss of gAtA6 in the β cell induces an intolerance to glucose on ageing (Pujadas et al., Sci Rep 2016).
MECHAnISMS DAMAgIng AnD REgEnERATIng PAnCREATIC ISLETS
Studies of the mechanisms damaging pancreatic islets have shown that exposure in the womb to bisphenol-A increases the mass of β cells during development, heightening the risk of developing diabetes as an adult (Garcia-Arevalo et al., Endocrinology 2016), and that administering taurine reverts the changes caused by a fat-rich diet on the circadian rhythm of mice (Figueroa et al., Sci Rep 2016).
PREVEnTIVE AnD THERAPEUTIC STRATEgIES In REgEnERATIVE MEDICInE, CELL
THERAPY AnD gEnE THERAPY
A new protocol has been developed for obtaining insulin-producing cells responding to glucose from mouse embryo cells (Salguero-Aranda et al., Cell Transplant 2016).
A contribution was made to drafting the document of scientific associations International Pancreas and Islet transplant Association (IPITA) and Transplantation Society (TTS) on the future of the therapy for replacing β cells in diabetes (Markmann et al., Transplantation 2016).
Clinical trial NCT01257776 was completed, displaying the positive effects of intra-arterial administration of mesenchymal stem cells in the enhancement of clinical treatment for the diabetic foot.
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Scientific programmes 17