Glucose-induced release of tumour necrosis factor-alpha from human placental and adipose tissues in gestational diabetes mellitus

M. T. Coughlan, K. Oliva, H. M. Georgiou, J. M.H. Permezel, G. E. Rice

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Abstract

Aims: The cytokine tumour necrosis factor-alpha (TNF-α) has been implicated in the pathogenesis of insulin resistance in Type 2 diabetes mellitus, but limited data are available in relation to gestational diabetes mellitus (GDM), a disease in which similar biochemical abnormalities exist. We investigated the effect of exogenous glucose on the release of TNF-α from placental and adipose (omental and subcutaneous) tissue obtained from normal pregnant women, and women with GDM. Methods: Human tissue explants were incubated for up to 24 h and TNF-α concentration in the incubation medium quantified by ELISA. The effect of normal (5 mmol/l) and high (15 and 25 mmol/l) glucose concentrations on the release of TNF-α was assessed. Results: In placental and subcutaneous adipose tissues obtained from women with GDM (n = 6), TNF-α release was significantly greater under conditions of high glucose compared with normal glucose (placenta, 25 mmol/l 5915.7 ± 2579.6 and 15 mmol/l 4547.1 ± 2039.1 vs. 5 mmol/l 1897.1 ± 545.5; subcutaneous adipose tissue, 25 mmol/l 423.5 ± 207.0 and 15 mmol/l 278.5 ± 138.7 vs. 5 mmol/l 65.3 ± 28.5 pg/mg protein; P < 0.05). In contrast, there was no stimulatory effect of high glucose on TNF-α release by tissues obtained from normal pregnant women (n = 6) (placenta, 25 mmol/l 1542.1 ± 486.2 and 15 mmol/l 4263.3 ± 2737.7 vs. 5 mmol/l 5422.4 ± 1599.0; subcutaneous adipose tissue, 25 mmol/l 189.8 ± 120.4 and 15 mmol/l 124.5 ± 32.3 vs. 5 mmol/l 217.9 ± 103.5 pg/mg protein). Conclusions: These observations suggest that tissues from patients with GDM release greater amounts of TNF-α in response to high glucose. As TNF-α has been previously implicated in the regulation of glucose and lipid metabolism, and of insulin resistance, these data are consistent with the hypothesis that TNF-α may be involved in the pathogenesis and/or progression of GDM.

Original languageEnglish
Pages (from-to)921-927
Number of pages7
JournalDiabetic Medicine
Volume18
Issue number11
DOIs
Publication statusPublished - 1 Dec 2001
Externally publishedYes

Keywords

  • Adipose tissue
  • Gestational diabetes mellitus
  • High glucose
  • Human placenta
  • Tumour necrosis factor-alpha

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