PMID- 21537415 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20110714 LR - 20211020 IS - 2233-6087 (Electronic) IS - 2233-6079 (Print) IS - 2233-6079 (Linking) VI - 35 IP - 1 DP - 2011 Feb TI - Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate. PG - 65-71 LID - 10.4093/dmj.2011.35.1.65 [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by increased levels of circulating fatty acid. Elevations in fatty acids and glucose for prolonged periods of time have been suggested to cause progressive dysfunction or apoptosis of pancreatic beta cells in T2DM. However, the precise mechanism of this adverse effect is not well understood. METHODS: INS-1 rat-derived insulin-secreting cells were exposed to 30 mM glucose and 0.25 mM palmitate for 48 hours. RESULTS: The production of reactive oxygen species increased significantly. Pancreatic and duodenal homeobox 1 (Pdx1) expression was down-regulated, as assessed by reverse transcription-polymerase chain reaction and Western blot analyses. The promoter activities of insulin and Pdx1 were also diminished. Of note, there was nucleocytoplasmic translocation of Pdx1, which was partially prevented by treatment with an antioxidant, N-acetyl-L-cysteine. CONCLUSION: Our data suggest that prolonged exposure of beta cells to elevated levels of glucose and palmitate negatively affects Pdx1 expression via oxidative stress. FAU - Ryu, Gyeong Ryul AU - Ryu GR AD - Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Yoo, Jun Mo AU - Yoo JM FAU - Lee, Esder AU - Lee E FAU - Ko, Seung-Hyun AU - Ko SH FAU - Ahn, Yu-Bae AU - Ahn YB FAU - Song, Ki-Ho AU - Song KH LA - eng PT - Journal Article DEP - 20110228 PL - Korea (South) TA - Diabetes Metab J JT - Diabetes & metabolism journal JID - 101556588 PMC - PMC3080567 OTO - NOTNLM OT - Fatty acid OT - High glucose OT - Insulin OT - Oxidative stress OT - Palmitate OT - Pancreatic beta cell OT - Pdx1 EDAT- 2011/05/04 06:00 MHDA- 2011/05/04 06:01 PMCR- 2011/02/01 CRDT- 2011/05/04 06:00 PHST- 2010/05/26 00:00 [received] PHST- 2010/09/28 00:00 [accepted] PHST- 2011/05/04 06:00 [entrez] PHST- 2011/05/04 06:00 [pubmed] PHST- 2011/05/04 06:01 [medline] PHST- 2011/02/01 00:00 [pmc-release] AID - 10.4093/dmj.2011.35.1.65 [doi] PST - ppublish SO - Diabetes Metab J. 2011 Feb;35(1):65-71. doi: 10.4093/dmj.2011.35.1.65. Epub 2011 Feb 28.