Diabetes & Metabolism Journal

Original Article

Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate: Gyeong Ryul Ryu, Jun Mo Yoo, Esder Lee, Seung-Hyun Ko, Yu-Bae Ahn, Ki-Ho Song; Diabetes Metab J. 2011;35(1):65-71. Published online February 28, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.1.65

3,517 View
39 Download
4 Crossref

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.

Citations

Citations to this article as recorded by

Nrf2 Activation Protects Mouse Beta Cells from Glucolipotoxicity by Restoring Mitochondrial Function and Physiological Redox Balance
Johanna Schultheis, Dirk Beckmann, Dennis Mulac, Lena Müller, Melanie Esselen, Martina Düfer
Oxidative Medicine and Cellular Longevity.2019; 2019: 1. CrossRef
Early overnutrition reduces Pdx1 expression and induces β cell failure in Swiss Webster mice
Maria M. Glavas, Queenie Hui, Eva Tudurí, Suheda Erener, Naomi L. Kasteel, James D. Johnson, Timothy J. Kieffer
Scientific Reports.2019;[Epub] CrossRef
Anti-diabetic effect of mulberry leaf polysaccharide by inhibiting pancreatic islet cell apoptosis and ameliorating insulin secretory capacity in diabetic rats
Yao Zhang, Chunjiu Ren, Guobing Lu, Zhimei Mu, Weizheng Cui, Huiju Gao, Yanwen Wang
International Immunopharmacology.2014; 22(1): 248. CrossRef
The Furan Fatty Acid Metabolite CMPF Is Elevated in Diabetes and Induces β Cell Dysfunction
Kacey J. Prentice, Lemieux Luu, Emma M. Allister, Ying Liu, Lucy S. Jun, Kyle W. Sloop, Alexandre B. Hardy, Li Wei, Weiping Jia, I. George Fantus, Douglas H. Sweet, Gary Sweeney, Ravi Retnakaran, Feihan F. Dai, Michael B. Wheeler
Cell Metabolism.2014; 19(4): 653. CrossRef

First
Prev
Page of 1
Next
Last

Search