PMID- 28008587 OWN - NLM STAT- MEDLINE DCOM- 20170317 LR - 20181202 IS - 1439-3646 (Electronic) IS - 0947-7349 (Linking) VI - 125 IP - 2 DP - 2017 Feb TI - Neutral Ceramidase Secreted Via Exosome Protects Against Palmitate-Induced Apoptosis in INS-1 Cells. PG - 130-135 LID - 10.1055/s-0042-116314 [doi] AB - Aims: To investigate the effects of neutral ceramidase (NCDase) packaged in exosomes that are secreted from beta-cells on free fatty acid (FFA)-induced beta-cells apoptosis and its role in regulation of sphingolipid-mediated signaling pathway. Methods: HPLC and Western blotting were performed to determine NCDase activity and expression. Annexin V-fluorescein-isothiocyanate/propidium iodide flow cytometry was used to assess apoptosis. Electrospray ionization tandem mass spectrometry was used for ceramide (Cer), sphingosine-1-phosphate (S1P), and sphingosine (SPH) determination. Results: INS-1 cells over-expressed NCDase secreted active NCDase via exosomes. Exosomes isolated from the cultured medium of INS-1 cells that oxpressed NCDase could ameliorate palmitate-induced apoptosis. Furthermore, the results showed that exosome-derived NCDase treatment reduced intracellular Cer/S1P ratio. Conclusions: beta-cell secreted active NCDase via exosome, the exosome-packaged-NCDase protected beta-cells from FFA-induced apoptosis through regulating sphingolipid metabolites and it might be a potential treatment for beta-cell lipotoxicity and type 2 diabetes. CI - (c) Georg Thieme Verlag KG Stuttgart . New York. FAU - Tang, S AU - Tang S AD - Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Luo, F AU - Luo F AD - Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Feng, Y M AU - Feng YM AD - Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Wei, X AU - Wei X AD - Endocrine and Diabetes Center, Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Branch of China Academy of Chinese Medical Science, Nanjing, China. FAU - Miao, H AU - Miao H AD - Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Lu, Y B AU - Lu YB AD - Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Tang, Y AU - Tang Y AD - Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Ding, D F AU - Ding DF AD - Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Jin, J F AU - Jin JF AD - China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, China. FAU - Zhu, Q AU - Zhu Q AD - Department of Endocrinology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. LA - eng PT - Journal Article DEP - 20161222 PL - Germany TA - Exp Clin Endocrinol Diabetes JT - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association JID - 9505926 RN - 0 (Sphingolipids) RN - 2V16EO95H1 (Palmitic Acid) RN - EC 3.5.1.23 (Neutral Ceramidase) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Cell Line MH - Diabetes Mellitus, Type 2/metabolism/pathology/therapy MH - Exosomes/*metabolism MH - Insulin-Secreting Cells/*metabolism/pathology MH - Neutral Ceramidase/*metabolism MH - Palmitic Acid/*toxicity MH - Rats MH - Sphingolipids/metabolism EDAT- 2016/12/23 06:00 MHDA- 2017/03/18 06:00 CRDT- 2016/12/24 06:00 PHST- 2016/12/23 06:00 [pubmed] PHST- 2017/03/18 06:00 [medline] PHST- 2016/12/24 06:00 [entrez] AID - 10.1055/s-0042-116314 [doi] PST - ppublish SO - Exp Clin Endocrinol Diabetes. 2017 Feb;125(2):130-135. doi: 10.1055/s-0042-116314. Epub 2016 Dec 22.