RESUMO
Extracellular vesicles (EVs) are implicated in the crosstalk between adipocytes and other metabolic organs, and an altered biological cargo has been observed in EVs from human obese adipose tissue (AT). Yet, the role of adipocyte-derived EVs in pancreatic ß cells remains to be determined. Here, we explored the effects of EVs released from adipocytes isolated from both rodents and humans and human AT explants on survival and function of pancreatic ß cells and human pancreatic islets. EVs from healthy 3T3-L1 adipocytes increased survival and proliferation and promoted insulin secretion in INS-1E ß cells and human pancreatic islets, both those untreated or exposed to cytokines or glucolipotoxicity, whereas EVs from inflamed adipocytes caused ß cell death and dysfunction. Human lean adipocyte-derived EVs produced similar beneficial effects, whereas EVs from obese AT explants were harmful for human EndoC-ßH3 ß cells. We observed differential expression of miRNAs in EVs from healthy and inflamed adipocytes, as well as alteration in signaling pathways and expression of ß cell genes, adipokines, and cytokines in recipient ß cells. These in vitro results suggest that, depending on the physiopathological state of AT, adipocyte-derived EVs may influence ß cell fate and function.
Assuntos
Adipócitos , Tecido Adiposo , Vesículas Extracelulares/metabolismo , Ilhotas Pancreáticas , Obesidade/metabolismo , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adulto , Animais , Feminino , Humanos , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Masculino , CamundongosRESUMO
OBJECTIVE: Carotid-femoral pulse wave velocity (PWV) is considered the gold standard for arterial stiffness assessment in clinical practice. A large number of devices to measure PWV have been developed and validated. We reviewed different validation studies of PWV estimation techniques and assessed their conformity to the Artery Society Guidelines and the American Heart Association recommendations. METHODS: Pubmed and Medline (1995-2017) were searched to identify PWV validation studies. Of the 96 article retrieved, 26 met the inclusion criteria. RESULTS: Several devices had been developed and validated to noninvasively measure arterial stiffness, using applanation tonometry (SphygmoCor, PulsePen), piezoelectric mechanotransducers (Complior), cuff-based oscillometry (Arteriograph, Vicorder and Mobil-O-Graph), photodiode sensors (pOpmètre) and devices assessing brachial-ankle pulse wave velocity and cardiac-ankle PWV. Ultrasound technique and MRI remain confined to clinical research. Good agreement was found with the Artery Society Guidelines. Two studies (Complior, SphygmoCor Xcel) showed best adherence with the guidelines. In Arteriograph, MRI, ultrasound and SphygmoCor Xcel validation studies sample size was smaller than the minimum suggested by the guidelines. High discrepancies between devices were shown in distance estimation: in two studies (Arteriograph, Complior) path length was estimated in conformity to the guidelines. Transit time was calculated using the intersecting tangent method, but in two studies (Vicorder, pOpmètre) best agreement was found using the maximum of the second derivative. Six studies reached the accuracy level 'excellent' defined in the Artery guidelines. CONCLUSION: Method to assess transit time and path length need validation in larger populations. Further studies are required in different risk population to implement clinical applicability of every device.