Advanced glycation end-products regulate extracellular matrix-adipocyte metabolic crosstalk in diabetes. Sci Rep 2019 Dec 24;9(1):19748
Date
12/26/2019Pubmed ID
31875018Pubmed Central ID
PMC6930305DOI
10.1038/s41598-019-56242-zScopus ID
2-s2.0-85077143807 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
The adipose tissue extracellular matrix (ECM) regulates adipocyte cellular metabolism and is altered in obesity and type 2 diabetes, but mechanisms underlying ECM-adipocyte metabolic crosstalk are poorly defined. Advanced glycation end-product (AGE) formation is increased in diabetes. AGE alter tissue function via direct effects on ECM and by binding scavenger receptors on multiple cell types and signaling through Rho GTPases. Our goal was to determine the role and underlying mechanisms of AGE in regulating human ECM-adipocyte metabolic crosstalk. Visceral adipocytes from diabetic and non-diabetic humans with obesity were studied in 2D and 3D-ECM culture systems. AGE is increased in adipose tissue from diabetic compared to non-diabetic subjects. Glycated collagen 1 and AGE-modified ECM regulate adipocyte glucose uptake and expression of AGE scavenger receptors and Rho signaling mediators, including the DIAPH1 gene, which encodes the human Diaphanous 1 protein (hDia1). Notably, inhibition of hDia1, but not scavenger receptors RAGE or CD36, attenuated AGE-ECM inhibition of adipocyte glucose uptake. These data demonstrate that AGE-modification of ECM contributes to adipocyte insulin resistance in human diabetes, and implicate hDia1 as a potential mediator of AGE-ECM-adipocyte metabolic crosstalk.
Author List
Strieder-Barboza C, Baker NA, Flesher CG, Karmakar M, Neeley CK, Polsinelli D, Dimick JB, Finks JF, Ghaferi AA, Varban OA, Lumeng CN, O'Rourke RWAuthor
Amir Ghaferi MD President, Phys Enterprise & SAD Clinical Affairs in the Medical College Physicians Administration department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdipocytesAdult
Aged
Diabetes Mellitus, Type 2
Extracellular Matrix
Female
Glycation End Products, Advanced
Humans
Insulin Resistance
Male
Middle Aged
Obesity
Receptor for Advanced Glycation End Products