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Association of Proteins Modulating Immune Response and Insulin Clearance During Gestation with Antenatal Complications in Patients with Gestational or Type 2 Diabetes Mellitus.

ABSTRACT: BACKGROUND:The purpose of the study is to establish and quantitatively assess protein markers and their combination in association with insulin uptake that may be have value for early prospective recognition of diabetic fetopathy (DF) as a complication in patients with diabetes mellitus during gestation. METHODS:Proteomic surveying and accurate quantitative measurement of selected proteins from plasma samples collected from the patients with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) who gave birth of either healthy or affected by maternal diabetes newborns was performed using mass spectrometry. RESULTS:We determined and quantitatively measured several proteins, including CRP, CEACAM1, CNDP1 and Ig-family that were significantly differed in patients that gave birth of newborns with signs of DF. We found that patients with newborns associated with DF are characterized by significantly decreased CEACAM1 (113.18 ± 16.23 ng/mL and 81.09 ± 10.54 ng/mL in GDM and T2DM, p < 0.005) in contrast to control group (515.6 ± 72.14 ng/mL, p < 0.005). On the contrary, the concentration of CNDP1 was increased in DF-associated groups and attained 49.3 ± 5.18 ng/mL and 37.7 ± 3.34 ng/mL (p < 0.005) in GDM and T2DM groups, respectively. Among other proteins, dramatically decreased concentration of IgG4 and IgA2 subclasses of immunoglobulins were noticed. CONCLUSION:The combination of the measured markers may assist (AUC = 0.893 (CI 95%, 0.785-0.980) in establishing the clinical finding of the developing DF especially in patients with GDM who are at the highest risk of chronic insulin resistance.

SUBMITTER: Kopylov AT

PROVIDER: S-EPMC7226479 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Association of Proteins Modulating Immune Response and Insulin Clearance During Gestation with Antenatal Complications in Patients with Gestational or Type 2 Diabetes Mellitus.

Kopylov Arthur T AT Kaysheva Anna L AL Papysheva Olga O Gribova Iveta I Kotaysch Galina G Kharitonova Lubov L Mayatskaya Tatiana T Krasheninnikova Anna A Morozov Sergey G SG

Cells 20200421 4

<h4>Background</h4>The purpose of the study is to establish and quantitatively assess protein markers and their combination in association with insulin uptake that may be have value for early prospective recognition of diabetic fetopathy (DF) as a complication in patients with diabetes mellitus during gestation.<h4>Methods</h4>Proteomic surveying and accurate quantitative measurement of selected proteins from plasma samples collected from the patients with gestational diabetes mellitus (GDM) and ...[more]

PMID: 32326243

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Project description:BackgroundInsulin resistance (IR) during gestational diabetes mellitus (GDM) has been linked to dysregulated insulin-PI3K/Akt pathway. A defective insulin-PI3K/Akt pathway and dysregulated circular RNA (circRNA) levels have been observed in the placentas of patients with GDM; however, the mechanisms underlying this association remain unclear.MethodscircRNAs potentially associated with GDM were selected through bioinformatics analysis and initially identified by quantitative real-time PCR (qPCR) in 9 GDM patients and 9 healthy controls, of which circMAP3K4 was further validated in additional 84 samples by qPCR. circMAP3K4 identity and localization were verified. Pearson correlation analysis was applied to evaluate the correlation between circMAP3K4 expression in the placental tissues of GDM patients and IR-related indicators. An IR model of trophoblasts was constructed using glucosamine. Interactions between miR-6795-5p and circMAP3K4 or PTPN1 were confirmed using a dual-luciferase reporter assay. The circMAP3K4/miR-6795-5p/PTPN1 axis and key markers in the insulin-PI3K/Akt pathway in placentas and trophoblasts were evaluated through qRT-PCR, immunofluorescence, and western blotting. The role of circMAP3K4 in glucose metabolism and cell growth in trophoblasts was determined using the glucose uptake and CCK8 assay, respectively.ResultscircMAP3K4 was highly expressed in the placentas of patients with GDM and the IR trophoblast model; this was associated with a dysregulated insulin-PI3K/Akt pathway. circMAP3K4 in the placentas of GDM patients was positively correlated with weight gain during pregnancy and time-glucose area under the curve of OGTT. circMAP3K4 and PTPN1 could both bind to miR-6795-5p. miR-6795-5p and PTPN1 were downregulated and upregulated, respectively, in the placentas of GDM patients and the IR trophoblast model. circMAP3K4 silencing or miR-6795-5p overexpression partially reversed the decrease in glucose uptake, inhibition in cell growth, and downregulated IRS1 and Akt phosphorylation in IR-trophoblasts; this restoration was reversed upon co-transfection with an miR-6795-5p inhibitor or PTPN1.ConclusioncircMAP3K4 could suppress the insulin-PI3K/Akt signaling pathway via miR-6795-5p/PTPN1 axis, probably contributing to GDM-related IR.

Dataset Information

Association of Proteins Modulating Immune Response and Insulin Clearance During Gestation with Antenatal Complications in Patients with Gestational or Type 2 Diabetes Mellitus.

Publications

Association of Proteins Modulating Immune Response and Insulin Clearance During Gestation with Antenatal Complications in Patients with Gestational or Type 2 Diabetes Mellitus.

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