Glucose-induced release of tumour necrosis factor-alpha from human placental and adipose tissues in gestational diabetes mellitus.
OBJECTIVE
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.
Coughlan
M T
MT
Department of Obstetrics and Gynaecology, The University of Melbourne, Mercy Hospital for Women, East Melbourne, Australia. m.coughlan@pgrad.unimelb.edu.au
Oliva
K
K
Georgiou
H M
HM
Permezel
J M
JM
Rice
G E
GE
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D015992:Body Mass Index; D017077:Culture Media, Conditioned; D046508:Culture Techniques; D016640:Diabetes, Gestational / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009852:Omentum; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone; D007770:L-Lactate Dehydrogenase; D005947:Glucose