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Cited by 163Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Glucocorticoids Down-Regulate Glucose Uptake Capacity and Insulin-Signaling Proteins in Omental But Not Subcutaneous Human Adipocytes

Lundgren, M., Burén, J., Ruge, T., Myrnäs, T., Eriksson, J. W.·2004·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2003-031157
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Abstract

Visceral adiposity is associated with insulin resistance and type 2 diabetes. This study explores the metabolic differences between s.c. and visceral fat depots with respect to effects in vitro of glucocorticoids and insulin on glucose uptake. Adipocytes from human s.c. and omental fat depots were obtained during abdominal surgery in 18 nondiabetic subjects. Cells were isolated, and metabolic studies were performed directly after the biopsies and after a culture period of 24 h with or without dexamethasone. After washing, basal and insulin-stimulated [14C]glucose uptake as well as cellular content of insulin signaling proteins and glucose transporter 4 (GLUT4) was assessed. Omental adipocytes had an approximately 2-fold higher rate of insulin-stimulated glucose uptake compared with s.c. adipocytes (P < 0.01). Dexamethasone treatment markedly inhibited (by approximately 50%; P < 0.05) both basal and insulin-stimulated glucose uptake in omental adipocytes but had no consistent effect in s.c. adipocytes. The cellular content of insulin receptor substrate 1 and phosphatidylinositol 3-kinase did not differ significantly between the depots, but the expression of protein kinase B (PKB) tended to be increased in omental compared with s.c. adipocytes (P = 0.09). Dexamethasone treatment decreased the expression of insulin receptor substrate 1 (by approximately 40%; P < 0.05) and PKB (by approximately 20%; P < 0.05) in omental but not in s.c. adipocytes. In contrast, dexamethasone pretreatment had no effect on insulin-stimulated Ser473 phosphorylation of PKB. GLUT4 expression was approximately 4-fold higher in omental than s.c. adipocytes (P < 0.05). Dexamethasone treatment did not alter the expression of GLUT4. In conclusion, human omental adipocytes display approximately 2-fold higher glucose uptake rate compared with s.c. adipocytes, and this could be explained by a higher GLUT4 expression. A marked suppression is exerted by glucocorticoids on glucose uptake and on the expression of insulin signaling proteins in omental but not in s.c. adipocytes. These findings may be of relevance for the interaction between endogenous glucocorticoids and visceral fat in the development of insulin resistance.

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Authors
Lundgren, M., Burén, J., Ruge, T., Myrnäs, T., & Eriksson, J. W.
Affiliations
  • Departments of Medicine (M.L., J.B., T.R., J.W.E.); SE-901 85, Sweden
  • Surgery (T.M.), Umeå University Hospital, Umeå SE-901 85, Sweden
Corresponding author
Eriksson, J. W.
ORCID
Ruge, T.
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2004-06-01
Volume
89
Issue
6
Pages
2989-2997
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2003-031157
OpenAlex
W2015237552
Semantic Scholar
3ac8ca39fe13f06f9ca60a9ec018ce4f020beaba
Cited by
163
References
58
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 7 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 13 · 2015: 6 · 2014: 7 · 2013: 11 · 2012: 8
FWCI
7.43
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
glucocorticoids, dexamethasone, glucose uptake, insulin signaling, omental adipocytes, subcutaneous adipocytes, visceral adipose tissue, GLUT4, IRS-1, phosphatidylinositol 3-kinase, Akt, insulin resistance, type 2 diabetes, adipocyte metabolism, insulin-stimulated glucose uptake
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Biological Transport, Carbon Radioisotopes, Cells, Cultured, Dexamethasone, Female, Glucocorticoids, Glucose, Humans, Insulin, Male, Middle Aged, Monosaccharide Transport Proteins, Muscle Proteins, Omentum, Signal Transduction, Adipocytes, Subcutaneous Tissue, Glucose Transporter Type 4

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