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

• Published in: Diabetic medicine Vol. 18; no. 11; pp. 921 - 927
• Main Authors: Coughlan, M. T., Oliva, K., Georgiou, H. M., Permezel, J. M. H., Rice, G. E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.11.2001; Blackwell
• Subjects: adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adult; Biological and medical sciences; Body Mass Index; Culture Media, Conditioned; Culture Techniques; Diabetes, Gestational - metabolism; Diabetes. Impaired glucose tolerance; Diseases of mother, fetus and pregnancy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme-Linked Immunosorbent Assay; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; gestational diabetes mellitus; Glucose - pharmacology; Gynecology. Andrology. Obstetrics; high glucose; human placenta; Humans; Kinetics; L-Lactate Dehydrogenase - metabolism; Medical sciences; Omentum; Placenta - drug effects; Placenta - metabolism; Pregnancy; Pregnancy. Fetus. Placenta; Progesterone - metabolism; Tumor Necrosis Factor-alpha - metabolism; tumour necrosis factor-alpha; Endocrinopathy; Human; Adipose tissue; Pregnancy disorders; Pathogenesis; Diabetes mellitus; Cytokine; Glucose; Pregnancy; Placenta; Female; Tumor necrosis factor α; Release
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1046/j.1464-5491.2001.00614.x

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. Diabet. Med. 18, 921–927 (2001)