AGE-induced interference of glucose uptake and transport as a possible cause of insulin resistance in adipocytes

Chi Hao Wu, Hsiao Wen Huang, Shang Ming Huang, Jer An Lin, Chi-Tai Yeh, Gow Chin Yen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The purpose of this study was to investigate the distinct roles of advanced glycation end products (AGEs) on insulin-mediated glucose disposal in 3T3-L1 adipocytes and C2C12 skeletal muscle cells. AGE-modified proteins, namely, GO-AGEs, were prepared by incubating bovine serum albumin (BSA) with glyoxal (GO) for 7 days. Glucose utilization rates and the expression of insulin signaling-associated proteins, including Akt, insulin receptor substrate-1, and glucose transporter 4, were determined. GO-AGEs caused insulin resistance (IR) by suppressing insulin-stimulated glucose uptake both in 3T3-L1 adipocytes and C2C12 muscle cells. Interestingly, an unexpected finding was that insulin-stimulated glucose transport in adipocytes was affected by GO-AGEs in a biphasic manner, with an initial steep increase (168%) during the first 8 h of incubation followed by a significantly impaired uptake after extended culture times (24-48 h, p <0.05). Treatment with GO-AGEs for 24 h markedly accelerated lipid droplet formation compared to the BSA control; however, it was blocked by incubation with an anti-RAGE antibody. Our study suggests that GO-AGEs induce an early dramatic elevation of glucose transport in adipocytes that may be related to the activation of insulin signaling; however, subsequent IR may result from increased oxidative stress and proinflammatory TNF-α production.

Original languageEnglish
Pages (from-to)7978-7984
Number of pages7
JournalJournal of Agricultural and Food Chemistry
Volume59
Issue number14
DOIs
Publication statusPublished - Jul 27 2011

Fingerprint

Glyoxal
adipocytes
Adipocytes
insulin resistance
Insulin Resistance
insulin
Insulin
uptake mechanisms
Glucose
glucose
bovine serum albumin
myocytes
Bovine Serum Albumin
Muscle Cells
Muscle
glucose transporters
Insulin Receptor Substrate Proteins
Cells
Advanced Glycosylation End Products
Facilitative Glucose Transport Proteins

Keywords

  • Adipocytes
  • advanced glycation end products
  • inflammation
  • insulin resistance
  • oxidative stress
  • receptor for AGEs

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

Cite this

AGE-induced interference of glucose uptake and transport as a possible cause of insulin resistance in adipocytes. / Wu, Chi Hao; Huang, Hsiao Wen; Huang, Shang Ming; Lin, Jer An; Yeh, Chi-Tai; Yen, Gow Chin.

In: Journal of Agricultural and Food Chemistry, Vol. 59, No. 14, 27.07.2011, p. 7978-7984.

Research output: Contribution to journalArticle

Wu, Chi Hao ; Huang, Hsiao Wen ; Huang, Shang Ming ; Lin, Jer An ; Yeh, Chi-Tai ; Yen, Gow Chin. / AGE-induced interference of glucose uptake and transport as a possible cause of insulin resistance in adipocytes. In: Journal of Agricultural and Food Chemistry. 2011 ; Vol. 59, No. 14. pp. 7978-7984.
@article{84128803483c4df78abdf5efc44d02bc,
title = "AGE-induced interference of glucose uptake and transport as a possible cause of insulin resistance in adipocytes",
abstract = "The purpose of this study was to investigate the distinct roles of advanced glycation end products (AGEs) on insulin-mediated glucose disposal in 3T3-L1 adipocytes and C2C12 skeletal muscle cells. AGE-modified proteins, namely, GO-AGEs, were prepared by incubating bovine serum albumin (BSA) with glyoxal (GO) for 7 days. Glucose utilization rates and the expression of insulin signaling-associated proteins, including Akt, insulin receptor substrate-1, and glucose transporter 4, were determined. GO-AGEs caused insulin resistance (IR) by suppressing insulin-stimulated glucose uptake both in 3T3-L1 adipocytes and C2C12 muscle cells. Interestingly, an unexpected finding was that insulin-stimulated glucose transport in adipocytes was affected by GO-AGEs in a biphasic manner, with an initial steep increase (168{\%}) during the first 8 h of incubation followed by a significantly impaired uptake after extended culture times (24-48 h, p <0.05). Treatment with GO-AGEs for 24 h markedly accelerated lipid droplet formation compared to the BSA control; however, it was blocked by incubation with an anti-RAGE antibody. Our study suggests that GO-AGEs induce an early dramatic elevation of glucose transport in adipocytes that may be related to the activation of insulin signaling; however, subsequent IR may result from increased oxidative stress and proinflammatory TNF-α production.",
keywords = "Adipocytes, advanced glycation end products, inflammation, insulin resistance, oxidative stress, receptor for AGEs",
author = "Wu, {Chi Hao} and Huang, {Hsiao Wen} and Huang, {Shang Ming} and Lin, {Jer An} and Chi-Tai Yeh and Yen, {Gow Chin}",
year = "2011",
month = "7",
day = "27",
doi = "10.1021/jf201271y",
language = "English",
volume = "59",
pages = "7978--7984",
journal = "Journal of Agricultural and Food Chemistry",
issn = "0021-8561",
publisher = "American Chemical Society",
number = "14",

}

TY - JOUR

T1 - AGE-induced interference of glucose uptake and transport as a possible cause of insulin resistance in adipocytes

AU - Wu, Chi Hao

AU - Huang, Hsiao Wen

AU - Huang, Shang Ming

AU - Lin, Jer An

AU - Yeh, Chi-Tai

AU - Yen, Gow Chin

PY - 2011/7/27

Y1 - 2011/7/27

N2 - The purpose of this study was to investigate the distinct roles of advanced glycation end products (AGEs) on insulin-mediated glucose disposal in 3T3-L1 adipocytes and C2C12 skeletal muscle cells. AGE-modified proteins, namely, GO-AGEs, were prepared by incubating bovine serum albumin (BSA) with glyoxal (GO) for 7 days. Glucose utilization rates and the expression of insulin signaling-associated proteins, including Akt, insulin receptor substrate-1, and glucose transporter 4, were determined. GO-AGEs caused insulin resistance (IR) by suppressing insulin-stimulated glucose uptake both in 3T3-L1 adipocytes and C2C12 muscle cells. Interestingly, an unexpected finding was that insulin-stimulated glucose transport in adipocytes was affected by GO-AGEs in a biphasic manner, with an initial steep increase (168%) during the first 8 h of incubation followed by a significantly impaired uptake after extended culture times (24-48 h, p <0.05). Treatment with GO-AGEs for 24 h markedly accelerated lipid droplet formation compared to the BSA control; however, it was blocked by incubation with an anti-RAGE antibody. Our study suggests that GO-AGEs induce an early dramatic elevation of glucose transport in adipocytes that may be related to the activation of insulin signaling; however, subsequent IR may result from increased oxidative stress and proinflammatory TNF-α production.

AB - The purpose of this study was to investigate the distinct roles of advanced glycation end products (AGEs) on insulin-mediated glucose disposal in 3T3-L1 adipocytes and C2C12 skeletal muscle cells. AGE-modified proteins, namely, GO-AGEs, were prepared by incubating bovine serum albumin (BSA) with glyoxal (GO) for 7 days. Glucose utilization rates and the expression of insulin signaling-associated proteins, including Akt, insulin receptor substrate-1, and glucose transporter 4, were determined. GO-AGEs caused insulin resistance (IR) by suppressing insulin-stimulated glucose uptake both in 3T3-L1 adipocytes and C2C12 muscle cells. Interestingly, an unexpected finding was that insulin-stimulated glucose transport in adipocytes was affected by GO-AGEs in a biphasic manner, with an initial steep increase (168%) during the first 8 h of incubation followed by a significantly impaired uptake after extended culture times (24-48 h, p <0.05). Treatment with GO-AGEs for 24 h markedly accelerated lipid droplet formation compared to the BSA control; however, it was blocked by incubation with an anti-RAGE antibody. Our study suggests that GO-AGEs induce an early dramatic elevation of glucose transport in adipocytes that may be related to the activation of insulin signaling; however, subsequent IR may result from increased oxidative stress and proinflammatory TNF-α production.

KW - Adipocytes

KW - advanced glycation end products

KW - inflammation

KW - insulin resistance

KW - oxidative stress

KW - receptor for AGEs

UR - http://www.scopus.com/inward/record.url?scp=79960607593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960607593&partnerID=8YFLogxK

U2 - 10.1021/jf201271y

DO - 10.1021/jf201271y

M3 - Article

C2 - 21650468

AN - SCOPUS:79960607593

VL - 59

SP - 7978

EP - 7984

JO - Journal of Agricultural and Food Chemistry

JF - Journal of Agricultural and Food Chemistry

SN - 0021-8561

IS - 14

ER -