High Glucose-Aggravated Hepatic Insulin Resistance: Role of the NLRP3 Inflammasome in Kupffer Cells

Obesity
Tao ZhengLi Chen

Abstract

This study aimed to investigate whether the NLRP3 inflammasome in Kupffer cells (KCs) can be activated in response to high glucose (HG) and to evaluate its influence on hepatic insulin sensitivity. Primary KCs and hepatocytes were isolated from mice, and lipid accumulation, glucose output, and insulin sensitivity of hepatocytes were investigated after culturing either alone or with KCs exposed to HG. The influence of HG-induced NLRP3 inflammasome activation in KCs on insulin sensitivity of hepatocytes was examined. Treatment with gadolinium trichloride caused KC depletion, and, subsequently, a streptozotocin-induced hyperglycemic mouse model was used to confirm the influence of KCs on hepatic insulin sensitivity. Hepatocytes cocultured with KCs showed enhanced lipid accumulation, glucose output, and impaired insulin sensitivity when exposed to HG. Enhanced NLRP3 inflammasome activation was also evident in both hepatocytes and KCs. Moreover, KCs that were pretreated with caspase-1 inhibitor, NLRP3 inhibitor, and NLRP3 small interfering RNA corrected coculture-induced aberrances in insulin action and NLRP3 inflammasome activation in hepatocytes. KC coculture also increased interleukin-1β (IL-1β)-mediated nuclear factor-κB (NF-κB)...Continue Reading

References

Feb 13, 2001·Environmental Toxicology and Pharmacology·M ItoA Naruse
Dec 15, 2006·World Journal of Gastroenterology : WJG·George KoliosElias Kouroumalis
Oct 31, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Nicolas LanthierIsabelle A Leclercq
Dec 22, 2009·Nature Immunology·Rongbin ZhouJürg Tschopp
Jan 11, 2011·Nature Medicine·Bolormaa VandanmagsarVishwa Deep Dixit
Feb 26, 2011·Journal of Pharmacology & Pharmacotherapeutics·Carol KilkennyDouglas G Altman
Jul 8, 2011·Trends in Immunology·Dominic De Nardo, Eicke Latz
Jul 9, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jinghong WanCatherine Pavoine
Aug 2, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hai HuangAllan Tsung
Jun 6, 2014·Nature·Rachel J PerryGerald I Shulman
Oct 21, 2014·Antioxidants & Redox Signaling·Justine M AbaisPin-Lan Li
Mar 26, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Michaela TencerovaMichael P Czech
Aug 25, 2015·Biochimica Et Biophysica Acta·Udayakumar KarunakaranKyu Chang Won
Jan 5, 2016·The Journal of Clinical Investigation·Varman T Samuel, Gerald I Shulman
Feb 13, 2016·Journal of Internal Medicine·J JagerM Aouadi
Jan 4, 2017·The Journal of Clinical Investigation·Alan R Saltiel, Jerrold M Olefsky
Feb 9, 2017·Journal of Hepatology·Auvro R MridhaGeoffrey C Farrell
Feb 10, 2017·Nature·Gökhan S Hotamisligil
Feb 10, 2017·Health Promotion International·UNKNOWN World Health Organization
Jul 12, 2017·Nature Medicine·Michael P Czech
Aug 3, 2017·Metabolism: Clinical and Experimental·Jakeline RheinheimerDaisy Crispim
Feb 23, 2019·The Journal of Clinical Endocrinology and Metabolism·Devjit TripathyRalph A DeFronzo

❮ Previous
Next ❯

Citations

Feb 10, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Bulbul AhmedMichael W Greene

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.