Insulin promotes vascular smooth muscle cell proliferation and apoptosis via differential regulation of tumor necrosis factor-related apoptosis-inducing ligand

Journal of Diabetes
Hanis H HarithMary M Kavurma

Abstract

Insulin regulates glucose homeostasis but can also promote vascular smooth muscle (VSMC) proliferation, important in atherogenesis. Recently, we showed that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) stimulates intimal thickening via accelerated growth of VSMCs. The aim of the present study was to determine whether insulin-induced effects on VSMCs occur via TRAIL. Expression of TRAIL and TRAIL receptor in response to insulin and glucose was determined by polymerase chain reaction. Transcriptional activity was assessed using wild-type and site-specific mutations of the TRAIL promoter. Chromatin immunoprecipitation studies were performed. VSMC proliferation and apoptosis was measured. Insulin and glucose exposure to VSMC for 24 h stimulated TRAIL mRNA expression. This was also evident at the transcriptional level. Both insulin- and glucose-inducible TRAIL transcriptional activity was blocked by dominant-negative specificity protein-1 (Sp1) overexpression. There are five functional Sp1-binding elements (Sp1-1, Sp1-2, Sp-5/6 and Sp1-7) on the TRAIL promoter. Insulin required the Sp1-1 and Sp1-2 sites, but glucose needed all Sp1-binding sites to induce transcription. Furthermore, insulin (but not glucose) was ab...Continue Reading

References

Jun 1, 1996·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·W J BanzM B Zemel
Aug 10, 2000·The Journal of Biological Chemistry·S VaulontA Kahn
Jul 11, 2002·American Journal of Physiology. Cell Physiology·Hiroya SakumaKeigo Yasuda
Nov 15, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·L BergandiA Bosia
Apr 6, 2005·Journal of the American College of Cardiology·Yoav MichowitzJacob George
Mar 14, 2007·Journal of Cellular Physiology·Federica CoralliniGiorgio Zauli
May 26, 2007·Endocrine Reviews·Ranganath MuniyappaMichael J Quon
Jan 6, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Niels EngberdingKathy K Griendling
Feb 24, 2009·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·E R IsenovicP Marche
Jun 19, 2009·Cardiovascular & Hematological Disorders Drug Targets·Esma R IsenovićPierre Marche
Jul 10, 2009·Methods in Molecular Biology·Joel NelsonKarol Bomsztyk
Dec 26, 2009·Thrombosis Research·Katsuhito MoriYoshiki Nishizawa
Mar 2, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Sophie LiabeufZiad A Massy
Dec 15, 2010·Circulation Research·Mark E Cooper, Assam El-Osta
Dec 17, 2010·Current Pharmaceutical Design·Esma R IsenovićPierre Marche
Apr 6, 2011·Journal of Molecular and Cellular Cardiology·Xing-Li SuXiu-Ling Deng

❮ Previous
Next ❯

Citations

Apr 6, 2019·Journal of Cellular and Molecular Medicine·Ce GuWen-Song Tan
Jun 6, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Siân P CartlandMary M Kavurma
Aug 14, 2018·Frontiers in Medicine·Adam T BraithwaiteAllan Lawrie

❮ Previous
Next ❯

Related Concepts

Related Feeds

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.

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