Insulin activates hypoxia-inducible factor-1alpha in human and rat vascular smooth muscle cells via phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways: impairment in insulin resistance owing to defects in insulin signalling

Diabetologia
Gabriella DoronzoMariella Trovati

Abstract

We previously demonstrated that insulin stimulates vascular endothelial growth factor (VEGF) synthesis and secretion via phosphatidylinositol-3 kinase (PI3-K) and mitogen-activated protein kinase (MAPK) pathways in vascular smooth muscle cells (VSMC) from humans and from insulin-sensitive lean Zucker fa/+ rats. We also showed that this effect is attenuated in VSMC from insulin-resistant obese Zucker fa/fa rats. As it is not known whether the effects of insulin on VEGF involve activation of hypoxia-inducible factor-1 (HIF-1), we aimed to evaluate: (1) whether insulin modulates HIF-1alpha protein synthesis and activity; (2) the insulin signalling pathways involved; and (3) the role of insulin resistance. Using aortic VSMC taken from humans and Zucker rats and cultured in normoxia, the following were evaluated: (1) dose-dependent (0.5, 1, 2 nmol/l) and time-dependent (2, 4, 6 h) effects exerted by insulin on HIF-1alpha content in both nucleus and cytosol, measured by Western blots; (2) insulin effects on HIF-1 DNA-binding activity on the VEGF gene, measured by electrophoretic mobility shift assay; and (3) involvement of the insulin signalling molecules in these insulin actions, by using the following inhibitors: LY294002 (PI3-K), ...Continue Reading

References

Jun 2, 1995·The Journal of Biological Chemistry·A P LevyM A Goldberg
Apr 17, 1997·Nature·W Risau
Feb 17, 2000·The Journal of Clinical Investigation·K CusiL J Mandarino
Mar 31, 2000·Nature Medicine·P Carmeliet
Apr 6, 2000·Journal of Applied Physiology·G L Semenza
Jun 6, 2000·The Journal of Biological Chemistry·D E RichardJ Pouyssegur
Feb 13, 2001·Journal of Applied Physiology·A A OsmanL J Mandarino
May 15, 2001·American Journal of Physiology. Cell Physiology·N Ferrara
Jul 18, 2002·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·S JonssonL Janzon
Oct 16, 2002·The Journal of Biological Chemistry·Elisabeth L PagéDarren E Richard
Jun 5, 2003·Nature Medicine·Christopher W Pugh, Peter J Ratcliffe
Nov 25, 2003·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·M B YilmazS Korkmaz
Jan 22, 2004·Journal of Molecular and Cellular Cardiology·E D de Muinck, M Simons
Jan 28, 2004·Circulation·Jaikirshan J KhatriZorina S Galis
Mar 20, 2004·Experimental & Molecular Medicine·Ji-Won LeeKyu-Won Kim
Jul 28, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Naoichiro HattanDorothee Weihrauch
Oct 20, 2004·Coronary Artery Disease·Matthias Heil, Wolfgang Schaper
Oct 27, 2004·Diabetes·Cecilia C Low WangBoris Draznin
Nov 10, 2004·The Journal of Cell Biology·Brendan D Manning
Dec 15, 2004·Trends in Cardiovascular Medicine·Seppo Ylä-HerttualaTuomas T Rissanen
Jan 25, 2005·Cardiovascular Research·Johannes Waltenberger
Mar 29, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Maria A PotenzaMonica Montagnani
May 18, 2005·Journal of Cardiovascular Pharmacology·Yvonne K HodgesLawrence D Horwitz

❮ Previous
Next ❯

Citations

May 5, 2010·The Journal of Clinical Investigation·Kim ChengJenny E Gunton
Sep 23, 2014·General and Comparative Endocrinology·Ajit SinghAmitabh Krishna
Jul 24, 2010·Mediators of Inflammation·Giovanni AnfossiMariella Trovati
Aug 19, 2009·Archives of Physiology and Biochemistry·Giovanni AnfossiMariella Trovati
Jan 25, 2016·Reproductive Biomedicine Online·Fabian LungerBeata Seeber
Feb 16, 2010·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Hee-Jung ShinByeong-Churl Jang
Nov 18, 2008·Biochemical and Biophysical Research Communications·Hye-Lim KimJong-Wan Park
Nov 26, 2008·Medical Hypotheses·Peng ZhangYusheng Wang
Nov 28, 2006·Biochemical and Biophysical Research Communications·Marc HeidbrederPeter Dominiak
Mar 5, 2019·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Ian Warbrick, Simon W Rabkin
Aug 19, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nadia A HasaneenHussein D Foda
Sep 3, 2013·Biological & Pharmaceutical Bulletin·Shuji GamohRyuichi Yamamoto
Oct 21, 2019·Neuropathology and Applied Neurobiology·H-Y ChiuW C Shyu
Aug 21, 2008·The Journal of Clinical Endocrinology and Metabolism·Nuria García de la TorreAniceto L Charro
Sep 1, 2007·Expert Review of Endocrinology & Metabolism·Hisashi Makino, Shin-Ichi Suga
Feb 20, 2021·Frontiers in Cell and Developmental Biology·Zhanhao SuHao Zhang
Nov 23, 2016·Molecular Aspects of Medicine·Luis SilvaLuis Sobrevia
Dec 22, 2020·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Perla Pérez-TreviñoNoemí García

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.