Insulin resistance disrupts cell integrity, mitochondrial function, and inflammatory signaling in lymphatic endothelium

Microcirculation : the Official Journal of the Microcirculatory Society, Inc
Yang LeeMariappan Muthuchamy

Abstract

Lymphatic vessel dysfunction and increased lymph leakage have been directly associated with several metabolic diseases. However, the underlying cellular mechanisms causing lymphatic dysfunction have not been determined. Aberrant insulin signaling affects the metabolic function of cells and consequently impairs tissue function. We hypothesized that insulin resistance in LECs decreases eNOS activity, disrupts barrier integrity increases permeability, and activates mitochondrial dysfunction and pro-inflammatory signaling pathways. LECs were treated with insulin and/or glucose to determine the mechanisms leading to insulin resistance. Acute insulin treatment increased eNOS phosphorylation and NO production in LECs via activation of the PI3K/Akt signaling pathway. Prolonged hyperglycemia and hyperinsulinemia induced insulin resistance in LECs. Insulin-resistant LECs produced less NO due to a decrease in eNOS phosphorylation and showed a significant decrease in impedance across an LEC monolayer that was associated with disruption in the adherence junctional proteins. Additionally, insulin resistance in LECs impaired mitochondrial function by decreasing basal-, maximal-, and ATP-linked OCRs and activated NF-κB nuclear translocation co...Continue Reading

References

Dec 1, 1990·Journal of Molecular and Cellular Cardiology·A KrützfeldtH M Piper
Nov 1, 1989·The Journal of Clinical Investigation·Y J YangR N Bergman
Mar 1, 1972·European Journal of Clinical Investigation·F Camu, E Rasio
Jul 1, 1993·Circulation Research·I KuroseD N Granger
Feb 17, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·C HermannS Dimmeler
Jan 12, 2002·Nature Medicine·Louise E ReynoldsKairbaan M Hodivala-Dilke
Jun 18, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Sheila E FrancisRichard O Hynes
May 3, 2003·The Journal of Clinical Investigation·David VicentC Ronald Kahn
May 21, 2003·Proceedings of the National Academy of Sciences of the United States of America·Peter Sartipy, David J Loskutoff
Jul 1, 1958·The American Journal of Physiology·R M PATTERSONH S MAYERSON
Jul 1, 1962·The American Journal of Physiology·H S MAYERSONP MAYERSON
Nov 11, 2003·The Journal of Pharmacy and Pharmacology·Martin J KingMarianna Foldvari
Aug 12, 2004·Free Radical Biology & Medicine·Victor Darley-Usmar
Oct 12, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Dan PredescuAsrar B Malik
May 3, 2005·The Journal of Clinical Investigation·Kathryn E Wellen, Gökhan S Hotamisligil
Sep 20, 2005·Nature Genetics·Natasha L HarveyGuillermo Oliver
Oct 27, 2005·American Journal of Physiology. Endocrinology and Metabolism·Aidar R GosmanovAbbas E Kitabchi
May 30, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Sarah Y Yuan
Jul 1, 2006·The Journal of Physiology·Olga Yu GashevaAnatoliy A Gashev
Aug 23, 2006·Cell·Adam J EnglerDennis E Discher
Nov 23, 2006·The Journal of Experimental Medicine·Louise A JohnsonDavid G Jackson
May 29, 2007·Microvascular Research·N GaudreaultE D W Moore
Jul 20, 2007·European Journal of Clinical Investigation·M ArtwohlS M Baumgartner-Parzer
Jul 27, 2007·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Richard M CubbonStephen B Wheatcroft
Sep 12, 2007·The Journal of Experimental Medicine·Peter BalukDonald M McDonald
Sep 28, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·David D'AlessioPatrick Tso
Sep 6, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Francis KimMichael W Schwartz
Feb 17, 2009·Angiogenesis·Sophie Astrof, Richard O Hynes

❮ Previous
Next ❯

Citations

Jun 6, 2020·Frontiers in Physiology·Raghu P KataruBabak J Mehrara
Sep 16, 2020·Cellular and Molecular Life Sciences : CMLS·Sudarshan BhattacharjeeHong Chen
Apr 17, 2020·Frontiers in Neuroscience·Vignayanandam Ravindernath MuddapuM Michael Gromiha
Jun 2, 2020·Frontiers in Physiology·Pieter R Norden, Tsutomu Kume
Dec 5, 2019·Frontiers in Physiology·Xinguo JiangStanley G Rockson
Dec 12, 2020·Medical Hypotheses·L KeithM Carmody
Feb 9, 2020·The American Journal of Pathology·Subhashree KumaravelSanjukta Chakraborty
Jul 25, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xiao-Wen DingJeganathan Ramesh Babu
Sep 1, 2021·Cell Death & Disease·Yanyan CaoLei Liu

❮ 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.

Related Papers

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Yang LeeMariappan Muthuchamy
Current Opinion in Nephrology and Hypertension
G E McVeigh
Biochemical and Biophysical Research Communications
Nino MuradashviliDavid Lominadze
Nihon rinsho. Japanese journal of clinical medicine
Yoshihiko Nishio
© 2022 Meta ULC. All rights reserved