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Sabina Baumgartner-Parzer, Oswald Wagner, Peter Nowotny, Heinrich Vierhapper and Werner Waldhäusl

Baumgartner-Parzer S, Wagner 0, Nowotny P, Vierhapper H, Waldhäusl W. Stimulation of endothelin-1 production by thrombin, but lack of interference by high ambient glucose in vitro. Eur J Endocrinol 1994;130:271–5. ISSN 0804–4643

Diabetic vascular disease is associated with a state of hypercoagulability and altered endothelial properties, leading to elevated plasma levels of endothelium-derived peptides and proteins, e.g. endothelin-1. von Willebrand factor or fibronectin. This study determined dynamic immunoreactive endothelin-1 secretion by human umbilical vein endothelial cells exposed to thrombin (5 × 106 mU/l) in the presence (40 mmol/l) and absence (5.5 mmol/l) of excessive glucose in the cell culture medium. Exposure to high glucose and thrombin concentrations was initiated after cell confluency and applied for 24 h for measurements of endothelin-1 and for 2 and 5 h for the determination of preproendothelin-1, von Willebrand factor and fibronectin messenger ribonucleic acid. Comparisons were made versus cells incubated with normal glucose concentrations or with high mannose or NaCl concentrations as osmotic control. Neither preproendothelin-1, fibronectin and von Willebrand factor messenger ribonucleic acid expression nor endothelin-1 release was affected by high concentrations of glucose, mannose or sodium chloride.

Sabina Baumgartner-Parzer, Department of Medicine III, Division of Endocrinology and Metabolism, Währinger Gürtel 18-20, 1090 Vienna, Austria

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Jelena Todoric, Ammon Handisurya, Thomas Perkmann, Bernhard Knapp, Oswald Wagner, Andrea Tura, Giovanni Pacini, Harald Esterbauer and Alexandra Kautzky-Willer

Objective

Progranulin (PGRN) was recently introduced as a novel marker of chronic inflammatory response in obesity and type 2 diabetes capable of directly affecting the insulin signaling pathway. This study aimed to investigate the role of PGRN in gestational diabetes mellitus (GDM), which is regarded as a model for early type 2 diabetes.

Methods

PGRN serum levels were measured in 90 pregnant women (45 GDM and 45 normal glucose tolerance (NGT)). In addition, PGRN was measured during a 2-h, 75 g oral glucose tolerance test in 20 pregnant women (ten GDM and ten NGT) and in 16 of them post partum (ten GDM and six NGT).

Results

PGRN concentrations were significantly higher in pregnant women compared with post partum levels (536.79±31.81 vs 241.53±8.86, P<0.001). Multivariate regression analyses showed a strong positive correlation of PGRN with estrogen and progesterone. The insulinogenic index, a marker of early insulin secretion, displayed a positive correlation with PGRN, both during and after pregnancy (R=0.47, P=0.034; R=0.63, P=0.012). HbA1c and the oral glucose insulin sensitivity index showed significant post partum associations with PGRN (R=0.43, P=0.049; R=−0.65, P=0.009).

Conclusions

PGRN concentrations are markedly lower after pregnancy regardless of the gestational glucose tolerance state. PGRN levels per se do not discriminate between mild GDM and NGT in pregnant women. Therefore, the development of GDM appears to be due to impaired β-cell function that is not related to PGRN effect.