Page 33 - CIBERDEM-2015-eng

Research groups
Most relevant scientific articles
ESCRIBANO O., GóMEZ-HERNáNDEZ A., DíAZ-CASTROVERDE S., NEVADO C., GARCíA G., OTERO Y.F. ET AL. Insulin recep- tor isoform A confers a higher proliferative capability to pancreatic beta cells enabling glucose availability and IGF-I signaling. Molecular and Cellular Endocrinology. 2015;409:82-91.
PERDOMO L., BENEIT N., OTERO Y.F., ESCRIBANO O., DíAZ-CAS- TROVERDE S., GóMEZ-HERNáNDEZ A. ET AL. Protective role
of oleic acid against cardiovascular insulin resistance and in the early and late cellular atherosclerotic process. Car- diovascular Diabetology. 2015.
FUENTES-ANTRAS J., PICATOSTE B., GóMEZ-HERNáNDEZ A., EGIDO J., TUNON J., LORENZO O.. Updating experimental models of diabetic cardiomyopathy. Journal of Diabetes Research. 2015;2015.
Highlights
We developed iLIRKO as mouse model of diabetic progression. Thus, we have demonstrated that the reconstitution in hepatic-specific manner of iLIRKO mice, with adenosassociated viruses bearing IRA or IRB, showed a differential effect. Thus, IRA reverted the diabetic phenotype as revealed by glucose intol- erance, circulating hyperinsulinemia, increased pan- creatic beta cell mass and fasting hyperglycemia. Those effects upon infection with RIB weremostly limited. In vitro, in hepatic cell lines,IRA, but not IRB, positively regulated the glycogen synthesis and ul- timately the glycogen content. Regarding the endo- crine pancreas and its elastoplasticity, we previous- ly demonstrated that autophagy was a protection mechanism against ER stress in pancreatic beta cells. More importantl,human amylin, but not rat amylin, inhibited the basal autophagy in insulinoma cells. Thus, pancreatic beta cells submitted to the ER stressor thapsigargin induced apoptosis in the presence of human amylin, but not in the presence of rat amylin.MEFs cells lacking TSC2 upregulated the mTORC1 signaling pathway and inhibited the autophagy and mitophagy. Those cells induced ap- optosis in response to the ER stressor thapsigargin or in response to oxidative stressor CCCP.
ApoE mice induced hypercholesterolemia and vas- cular lesion. The double KO BATIRKO/ApoE aggra- vated the vascular damage owing to the failure of in- sulin secretion in response to the insulin resistance induced by HFD western diet.
Finally, we have characterized the phenotype of the IGFIR brown adipose tissue-specific KO (BATIG- FIRKO). KO mice showed a normal brown adipose tissue development likely due to the enhanced cir- culating levels of IGFI, but not BMP-7. However, those mice showed a significant impairment to cold acclimatation at 12 h. owing to the loss of UCP-1 at the canonical brown adipose tissue and at the beige cell within the inguinal white adipose tissue. At 12 months, they developed a significant insulin resistance owing to a sever insulin resistance in the liver. However, the insulin sensitivity in the brown ad- ipose tissue and in several compartments of white adipose tissue remained mostly unchanged.
Institution: Universidad Complutense de Madrid · Contact: Facultad de Farmacia Ciudad Universitaria, S/N. 28040 Madrid · Tel.: 91 394 17 77 · E.mail: [email protected] Website: http://www.ciberdem.org
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