Aims: The cytokine tumour necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha 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-alpha was assessed.
Results: In placental and subcutaneous adipose tissues obtained from women with GDM (n = 6), TNF-alpha 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-alpha 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-alpha in response to high glucose. As TNF-alpha 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-alpha may be involved in the pathogenesis and/or progression of GDM.