Abstract
AimThe aim of the study was to compare maternal and cord blood levels of betatrophin – a new peptide potentially controlling beta cell growth - as well as in its mRNA expression in subcutaneous adipose tissue, visceral adipose tissue and placental tissue obtained from pregnant women with normal glucose tolerance (NGT) and gestational diabetes (GDM).MethodsSerum betatrophin and irisin concentrations were measured by ELISA in 93 patients with GDM and 97 women with NGT between 24 and 28 week of gestation. Additionally, maternal and cord blood betatrophin and irisin, as well as their genes (C19orf80 and Fndc5) expression were evaluated in 20 patients with GDM and 20 women with NGT at term.ResultsIn both groups, serum betatrophin concentrations were significantly higher in the patients with GDM than in the controls (1.91 [1.40-2.60] ng/ml vs 1.63 [1.21-2.22] ng/ml, p=0.03 and 3.45 [2.77-6.53] ng/ml vs 2.78 [2.16-3.65] ng/ml, p=0.03, respectively). Cord blood betatrophin levels were also higher in the GDM than in the NGT group (20.43 [12.97-28.80] ng/ml vs 15.06 [10.11-21.36] ng/ml, p=0.03). In both groups betatrophin concentrations in arterial cord blood were significantly higher than in maternal serum (p=0.0001). Serum irisin levels were significantly lower in the patients with GDM (1679 [1308-2171] ng/ml) than in the healthy women between 24 and 28 week of pregnancy (1880 [1519-2312] ng/ml, p=0.03). Both C19orf80 and Fndc5 mRNA expression in fat and placental tissue did not differ significantly between the groups studied.ConclusionsOur results suggest that an increase in maternal and cord blood betatrophin might be a compensatory mechanism for enhanced insulin demand in GDM.
Highlights
Betatrophin, known as lipasin [1, 2], atypical angiopoietin like protein 8 (ANGPTL8) [3], refeeding induced fat and liver protein (RIFL) [4] and chromosome 19 open reading frame 80 (C19orf80), is a secreted protein of 198 amino acids, primarily expressed in the liver and adipose tissue [3, 4, 5]
Serum betatrophin concentrations were significantly higher in the patients with gestational diabetes mellitus (GDM) than in the controls (1.91 [1.40-2.60] ng/ml vs 1.63 [1.21-2.22] ng/ml, p=0.03 and 3.45 [2.77-6.53] ng/ml vs 2.78 [2.16-3.65] ng/ml, p=0.03, respectively)
Cord blood betatrophin levels were higher in the GDM than in the normal glucose tolerance (NGT) group (20.43 [12.97-28.80] ng/ml vs 15.06 [10.11-21.36] ng/ml, p=0.03)
Summary
Betatrophin, known as lipasin [1, 2], atypical angiopoietin like protein 8 (ANGPTL8) [3], refeeding induced fat and liver protein (RIFL) [4] and chromosome 19 open reading frame 80 (C19orf80), is a secreted protein of 198 amino acids, primarily expressed in the liver and adipose tissue [3, 4, 5]. Betatrophin was shown to promote pancreatic beta-cell proliferation, expand beta-cell mass and improve glucose tolerance in an animal model of insulin resistance caused by an insulin receptor antagonist S961 infusion [5]. Recently Zhang et al [10] reported that betatrophin gene (Gm6484/C19orf80) expression in primary rat adipocytes and 3T3-L1-derived adipocytes may be up-regulated by irisin—a novel myokine and adipokine [11, 12] encoded by Fndc (fibronectin type III domain containing 5) gene, which induces browning of white adipose tissue, thereby increasing total body energy expenditure and improving glucose tolerance in experimental animals [11]. Clinical studies have shown increased [9, 13,14,15,16,17,18], and unchanged [19] or even decreased [20] circulating betatrophin levels in patients with obesity and type 1 or type 2 diabetes in comparison with healthy individuals
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