Role of the transcriptional factor C/EBPbeta in free fatty acid-elicited beta-cell failure

Molecular and Cellular Endocrinology
Valérie PlaisanceRomano Regazzi

Abstract

Fatty acids can favour the development of Type 2 diabetes by reducing insulin secretion and inducing apoptosis of pancreatic beta-cells. Here, we show that sustained exposure of the beta-cell line MIN6 or of isolated pancreatic islets to the most abundant circulating fatty acid palmitate increases the level of C/EBPbeta, an insulin transcriptional repressor. In contrast, two unsaturated fatty acids, oleate and linoleate were without effect. The induction of C/EBPbeta elicited by palmitate was prevented by inhibiting the ERK1/2 MAP kinase pathway or by reducing mitochondrial fatty acid oxidation with an inhibitor of Carnitine Palmitoyl Transferase-1. Overexpression of C/EBPbeta mimicked the detrimental effects of palmitate and resulted in a drastic reduction in insulin promoter activity, impairment in the capacity to respond to secretory stimuli and an increase in apoptosis. Our data suggest a potential involvement of C/EBPbeta as mediator of the deleterious effects of unsaturated free fatty acids on beta-cell function.

References

May 1, 1989·Diabetes/metabolism Reviews·J D McGarryD W Foster
Dec 1, 1986·Transplantation·R SuttonP J Morris
Jan 1, 1985·Survey and Synthesis of Pathology Research·G KlöppelP U Heitz
Mar 1, 1996·European Journal of Endocrinology·M Prentki
Jan 17, 1997·The Journal of Biological Chemistry·F Assimacopoulos-JeannetM Prentki
Feb 15, 1997·European Journal of Biochemistry·J D McGarry, N F Brown
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·M ShimabukuroR H Unger
Jan 23, 1999·The Journal of Clinical Investigation·M IgarashiG L King
Jan 23, 1999·The Journal of Clinical Investigation·S LiuJ E Friedman
Sep 16, 1999·Cellular and Molecular Life Sciences : CMLS·L A Tibbles, J R Woodgett
Jun 1, 2000·Journal of Molecular Endocrinology·S Bonner-Weir
Jun 1, 2000·Endocrinology·S Bonner-Weir
Oct 29, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C BlázquezM Guzmán
Mar 30, 2001·The Journal of Biological Chemistry·L L ListenbergerJ E Schaffer
Jul 21, 2001·Molecular and Cellular Biology·J Y Yang, C Widmann
Dec 26, 2001·The Journal of Biological Chemistry·Marta Cortés-CanteliAna Perez-Castillo
May 15, 2002·The Biochemical Journal·Dipak P Ramji, Pelagia Foka
Jul 20, 2002·Trends in Molecular Medicine·Melissa K LingohrChristopher J Rhodes
Dec 28, 2002·Diabetes·Alexandra E ButlerPeter C Butler
Dec 20, 2003·The Journal of Biological Chemistry·Christoph F A VogelFumio Matsumura

❮ Previous
Next ❯

Citations

Dec 3, 2014·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Jelena MarkovićMelita Vidaković
Jan 23, 2015·Journal of Diabetes Research·Valérie PlaisanceAmar Abderrahmani
Dec 15, 2015·Journal of Diabetes Research·Saška BrajkovicAmar Abderrahmani
Sep 15, 2016·International Journal of Molecular Sciences·Jan ŠrámekJan Kovář
Feb 5, 2011·Diabetes/metabolism Research and Reviews·Zhenping LiuKjeld Hermansen
Mar 19, 2020·Cells·Justin Hou Ming Yung, Adria Giacca
Jul 29, 2020·International Journal of Molecular Sciences·Paloma Lillo UrzúaSergio Wehinger
Oct 20, 2019·Journal of Molecular Biology·Maria LytriviMiriam Cnop
May 1, 2021·International Journal of Molecular Sciences·Jan ŠrámekJan Kovář
Sep 1, 2009·Biochimica Et Biophysica Acta·Vincent PoitoutGhislaine Fontés

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis