Serum levels of the adipokine Pref-1 in gestational diabetes mellitus

Wurst, Ulrike; Ebert, Thomas; Kralisch, Susan; Stümvoll, Michael; Faßhauer, Mathias

doi:10.1016/j.cyto.2014.10.015

Cited by 17 publications

(13 citation statements)

References 30 publications

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“…Our results with the healthy non-diabetic cohorts supports previous studies correlating DLK1 positively to insulin resistance in non-healthy or mixed (healthy/non-healthy) cohorts [14,19,20,54,55]. Interestingly, using similar or alternative approaches other groups have shown the opposite [18,22,40,56] or no association [57]. Of these, Flehmig and co-workers [56] used a distance-based hierarchical cluster analysis approach to find patterns between serum adipokine levels and clinical parameters related to obesity, inflammation and glucose metabolism.…”

Section: Discussionsupporting

confidence: 90%

The imprinted gene Delta like non-canonical notch ligand 1 (Dlk1) associates with obesity and triggers insulin resistance through inhibition of skeletal muscle glucose uptake

et al. 2019

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Background The imprinted gene Delta like non-canonical Notch ligand 1 ( Dlk1 ) is considered an inhibitor of adipogenesis, but its in vivo impact on fat mass indeed remains elusive and controversial. Methods Fat deposits were assessed by MRI and DXA scanning in two cohorts of non-diabetic men, whereas glucose disposal rate (GDR) was determined during euglycemic hyperinsulinemic clamp. Blood analyte measurements were used for correlation and mediation analysis to investigate how age, BMI, and fat percentage affect the relation between DLK1 and GDR. Confirmatory animal studies performed in normal (NC) and high fat diet (HFD) fed Dlk1 +/+ and Dlk1 −/− mice included DXA scanning, glucose tolerance tests (GTTs), blood measurements, and skeletal muscle glucose uptake studies by positron emission tomography (PET), histology, qRT-PCR, and in vitro cell studies. Findings Overall, DLK1 is positively correlated with fat amounts, which is consistent with a negative linear relationship between DLK1 and GDR. This relationship is not mediated by age, BMI, or fat percentage. In support, DLK1 also correlates positively with HOMA-IR and ADIPO-IR in these humans, but has no linear relationship with the early diabetic inflammation marker MCP-1. In Dlk1 −/− mice, the increase in fat percentage and adipocyte size induced by HFD is attenuated, and these animals are protected against insulin resistance. These Dlk1 effects seem independent of gluconeogenesis, but at least partly relies on increased in vivo glucose uptake in skeletal muscles by Dlk1 regulating the major glucose transporter Glut4 in vivo as well as in two independent cell lines. Interpretation Thus, instead of an adipogenic inhibitor, Dlk1 should be regarded as a factor causally linked to obesity and insulin resistance, and may be used to predict development of type 2 diabetes. Fund The Danish Diabetes Academy supported by the , (#09-073648), The , , and , , , the Strategic Research Program in Diabetes at and an grant.

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Section: Discussionsupporting

confidence: 90%

The imprinted gene Delta like non-canonical notch ligand 1 (Dlk1) associates with obesity and triggers insulin resistance through inhibition of skeletal muscle glucose uptake

et al. 2019

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“…Mouse models with increased circulating dlk1 concentrations exhibit increased growth hormone secretion and igf-i resistance ( 31 ), and decreased muscular Glut4 expression ( 29 ), which provides a putative mechanism for DLK1-stimulated insulin resistance. Despite its associations with fasting insulin resistance and compensatory hyperinsulinemia, we found no association between circulating DLK1 levels and maternal glycaemia or GDM risk, which is consistent with the findings of Wurst et al ( 32 ). Li et al ( 33 ) found lower DLK1 concentrations were associated with GDM, but this was in cord blood in only a small number of pregnancies.…”

Section: Discussionsupporting

confidence: 92%

Pregnancy Serum DLK1 Concentrations Are Associated With Indices of Insulin Resistance and Secretion

Petry

Burling

Barker

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context DLK1 (delta like non-canonical notch ligand 1) is a paternally-expressed imprinted gene that encodes an epidermal growth factor repeat-containing transmembrane protein. A bioactive, truncated DLK1 protein is present in the circulation, and has roles in development and metabolism. Objective We sought to investigate links between maternal pregnancy circulating DLK1 concentrations and: (1) maternal and fetal DLK1 genotypes, (2) maternal insulin resistance and secretion and (3) offspring size at birth. Patients, design and setting We measured third trimester maternal serum DLK1 concentrations and examined their associations with parentally-transmitted fetal and maternal DLK1 genotypes, indices of maternal insulin resistance and secretion derived from 75g oral glucose tolerance tests performed around week 28 of pregnancy, and offspring size at birth in 613 pregnancies from the Cambridge Baby Growth Study. Results Maternal DLK1 concentrations were associated with the paternally-transmitted fetal DLK1 rs12147008 allele (p=7.8x10 -3) but not with maternal rs12147008 genotype (p=0.4). Maternal DLK1 concentrations were positively associated with maternal pre-pregnancy BMI (p=3.5x10 6), and (after adjustment for maternal BMI) with both maternal fasting insulin resistance (HOMA IR: p=0.01) and measures of maternal insulin secretion in response to oral glucose (insulinogenic index: p=1.2x10 -3; insulin disposition index: p=0.049). Further positive associations were found with offspring weight (p=0.02) and head circumference at birth (p=0.04). Conclusion These results are consistent with a partial paternal or placental origin for the maternal circulating DLK1 which may lead to increased maternal circulating DLK1 concentrations, stimulation of maternal insulin resistance and compensatory hyperinsulinemia during pregnancy, and the promotion of fetal growth.

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“…Later, Wurst et al assessed the DLK1 level among pregnant women with GDM, but contrary to their hypothesis, they did not detect any difference in GDM compared to the control group. Besides, the negative correlation between DLK1 levels and BMI and Creactive protein (CRP) is remarkable [23]. The fact that GDM is an inflammatory process, and women with GDM are predisposed to be more obese might corroborate the lower DLK1 in pregnant women with GDM in our study.…”

Section: Discussionsupporting

confidence: 75%

Maternal Serum Delta-Like 1 and Nesfatin-1 Levels in Gestational Diabetes Mellitus: A Prospective Case-Control Study

Çaltekin¹,

Caniklioğlu²

2021

Cureus

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Delta-like 1 (DLK1) and nesfatin-1 are adipokines that have been shown to affect glucose metabolism. We aimed to search serum DLK1 and nesfatin-1 concentrations at 24-28 weeks of pregnancy in women newly defined with gestational diabetes mellitus (GDM) and investigate the relationship of these adipokines with various metabolic parameters. MethodsSerum levels of DLK1 and nesfatin-1 were evaluated in 44 women with GDM, and in 40 healthy pregnant women by enzyme-linked immunosorbent assay (ELISA) kits. While performing oral glucose tolerance test (OGTT) for GDM diagnosis at 24-28 weeks of pregnancy, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profiles, glycosylated hemoglobin (HbA1c) were also measured. ResultsMaternal serum DLK1 and nesfatin-1 concentrations were found lower in pregnant women with GDM compared with healthy pregnant women (418.4±282.6 vs. 586.7±303 ng/L, p=0.002; 12.2±7.6 vs. 26.7±16.4 ng/ml, p<0.001, respectively). Maternal serum DLK1 levels correlated positively with HOMA-IR and fasting insulin (r=0.395, p=0.008; r=0.374, p=0.012, respectively). ConclusionWe determined that DLK1 and nesfatin-1 levels were lower in GDM. Based on this study, it may be considered that DLK1 could be culpable for metabolic disorders in GDM.

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Serum levels of the adipokine Pref-1 in gestational diabetes mellitus

Cited by 17 publications

References 30 publications

The imprinted gene Delta like non-canonical notch ligand 1 (Dlk1) associates with obesity and triggers insulin resistance through inhibition of skeletal muscle glucose uptake

The imprinted gene Delta like non-canonical notch ligand 1 (Dlk1) associates with obesity and triggers insulin resistance through inhibition of skeletal muscle glucose uptake

Pregnancy Serum DLK1 Concentrations Are Associated With Indices of Insulin Resistance and Secretion

Maternal Serum Delta-Like 1 and Nesfatin-1 Levels in Gestational Diabetes Mellitus: A Prospective Case-Control Study

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