Page 17 - CIBERDEM-2015-eng

Scientific Programmes
PROGRAMA 2. Molecular and cellular determinants of the function, damage and protection of pancreatic islets. Regenerative medicine and advanced therapies.
1. Function and regulation of pancreatic islets: molecular and cellular bases and therapeutic targets.
A new mechanism for autochrine action of pancre- atic peptide IAPP on the proliferative capacity of the beta cell (Visa et al., FASEB J. 2015) and the role of enzyme BACE2, on the insulin secretory function, as well as its potential use as a therapeutic target (Alcarraz-Vizán et al., FASEB J. 2015). Furthermore a set of mirRNAs correlating with prediabetes and fatty liver in humans and animals has been identi- fied (Parrizas et al., J Clin Endocrinol Metab 2015). It has also been shown that these mirRNAs become modify with the implementation of a programme of physical exercise.
A molecular mechanism by means of which the expression of the glucagon gene is repressed as a response to increases in the levels of blood glucose, thus helping to maintain glucose homeostasis, has been discovered and characterised. (Mirasierra and Vallejo, Diabetologia 2015).
It has been established that human islets have greater functional capacity and survive better in a culture medium supplemented with human serum against human albumin which enables improving the prognosis when these islets are transplanted later (Nacher et al., Cell Transplant. 2015).
It has been set up a protocol for differentiating hu- man embryonic stem cells which improves the final stages of differentiation and maturation of endocrine progenitors, enabling a large number of completely functional insulin-producing cells to be obtained (Pezzolla et al., PloS One 2015).
2. Mechanisms damaging and
regenerating pancreatic islets.
A map of “enhancers” active in human embryonic progenitors has been created and validated, ena- bling extending the list of active “enhancers” known in the embryonic pancreas (Cebola et al., Nat Cell Biol. 2015).
Defective processing of the α-MSH is a fundamental mediator of increased in gluconeogenesis which is observed in the setting of stress of the hypothalamic endoplasmic reticulum. The α-MSH deficit in POMC neurons can also contribute to the pathophysiology of diabetes mellitus type 2 (Schneeberger et al., Cell Rep. 2015).
3. Preventive and therapeutic strategies in regenerative medicine, cell therapy and gene therapy.
A moderately hypercaloric diet, after a situation of early nutritional restriction does not induce obesity but worsens insulin-resistance, dyslipidaemia and the proportion of ectopic lipids (Lizárraga-Mo- lline- do et al., J Biol Chem. 2015). Furthermore, a cocoa flavanol –rich diet prevents oxidative stress and the cell death appearing in pancreatic and hepatic insu- lin resistance, improving glucidic metabolism and preventing the loss of the function and mass of beta cells (Cordero-Herrera et al., J Nutr Biochem. 2015).
At the outset of obesity, caused by a fat-rich diet, there is a functional and structural adaptation of the pancreatic alpha cell which leads to a hypoglucag- onaemia, which could have a positive influence on the adaptation of the pancreas to obesity, to main- tain the homeostasis of glucose and prevent/delay the potential appearance of diabetes (Merino et al., Sci Rep. 2015). We have also shown that exposure to endocrine disruptors during pregnancy increases the mother’s predisposition to undergoing obesity and di- abetes throughout her life (Alonso-Magdalena et al., Endocrinology 2015).
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