scholarly journals Astragaloside IV attenuates gestational diabetes mellitus via targeting NLRP3 inflammasome in genetic mice

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Ruixue Zhang ◽  
Xuelei Zhang ◽  
Baoheng Xing ◽  
Jianyong Zhao ◽  
Peipei Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Nlrp3 Inflammasome ◽  
Mrna Levels ◽  
Mice Model ◽  
Astragaloside Iv ◽  
Necrosis Factor Alpha ◽  
Pyrin Domain ◽  
Tnf Α

Abstract Background As the most ordinary metabolic disorder during pregnancy, gestational diabetes mellitus (GDM) has become a severe risk for the health of both pregnant female and fetus. Astragaloside IV (AS-IV) is the dominant active component in Astragalus membranaceus. It has been proved that AS-IV has anti-inflammation and immune-regulation function. We aimed to demonstrate the function of AS-IV in the therapy of GDM and the molecular mechanism in this process. Methods C57BL/KsJ-Lepdb/+ female mice were used as GDM model. The mRNA levels of relative genes in this research were detected by qRT-PCR. The protein levels of relative genes were analyzed by western blot. Serum concentration of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were analyzed by ELISA. Results Glucose and insulin levels in GDM mice model were decreased by AS-IV treatment. AS-IV down-regulated the expression of inflammatory gene IL-6 and TNF-α in GDM mice model. AS-IV treatment inhibited the expression of NLR family pyrin domain containing-3 (NLRP3) inflammasome relative proteins in the pancreas of GDM mice. Conclusion This study demonstrated that AS-IV treatment has an effective therapeutic function of GDM in mice model through the inhibition of NLRP3 inflammasome in the pancreas.

Astragaloside IV relieves gestational diabetes mellitus in genetic mice through reducing hepatic gluconeogenesis

2020 ◽  
Vol 98 (7) ◽  
pp. 466-472
Author(s):  
Ruixue Zhang ◽  
Baoheng Xing ◽  
Jianyong Zhao ◽  
Xuelei Zhang ◽  
Ling Zhou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Lipid Level ◽  
Serum Lipid Level ◽  
Mrna Levels ◽  
Camp Accumulation ◽  
Mice Model ◽  
Astragaloside Iv ◽  
Hepatic Gluconeogenesis

The glucose intolerance developed during pregnancy is called gestational diabetes mellitus (GDM). GDM has become a severe risk for the health of both mother and baby. Astragaloside IV (AS-IV) is the dominant active component in Astragalus membranaceus and has been reported to have anti-inflammation and immune-regulation function. We aimed to demonstrate the function of AS-IV in the therapy of GDM and the molecular mechanism in this process. C57BL/KsJ-Lepdb/+ female mice were used as the GDM model. The mRNA levels of relative genes in this research were detected by quantitative real-time PCR. The protein levels of relative genes were analyzed by Western blot. Serum lipid level was measured with an ILab Chemistry Analyzer 300 PLUS. Glucose, insulin, and lipid profile levels in the GDM mice model were decreased by AS-IV treatment. AS-IV downregulated the expression of inflammatory genes and upregulated the expressions of anti-oxidant genes in the GDM mice model. AS-IV treatment reduced cAMP accumulation in liver and reduced hepatic gluconeogenesis in GDM mice. This study demonstrated that AS-IV treatment has an effective therapeutic function of GDM in a mice model through the regulation of cAMP accumulation and hepatic gluconeogenesis.

Blockade of CCL2/CCR2 Signaling Pathway Exerts Anti-Inflammatory Effects and Attenuates Gestational Diabetes Mellitus in a Genetic Mice Model

2020 ◽  
Vol 53 (01) ◽  
pp. 56-62
Author(s):  
Xinying Qi ◽  
Yanping Xing ◽  
Xuezhen Wang
Keyword(s):  
Diabetes Mellitus ◽  
Flow Cytometry ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Inflammatory Cytokines ◽  
Serum Insulin ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mice Model ◽  
Reverse Transcription Pcr ◽  
Tnf Α

AbstractThe chemokine (C-C motif) ligand 2 (CCL2) and its receptor CCR2 are involved in gestational diabetes mellitus (GDM). The present study aims to explore the effects of CCL2 blocking on GDM. Serum CCL2, interleukin (IL)-6, and tumor necrosis factor (TNF)-α were determined in GDM patients and healthy volunteers. C57BL/KsJdb/+mouse was used as the GDM model and CCL2 antibody (αCCL2) was applied. Flow cytometry was applied to determine the frequency of macrophages. Quantitative reverse transcription PCR (RT-qPCR) and western blot were determined to detect the mRNA and protein expressions, respectively. Enzyme-linked immunosorbent assay (ELISA) was applied to determine the levels of inflammatory cytokines and serum insulin. Serum CCL2 was correlated with inflammatory cytokines (IL-6 and TNF-α) in the GDM patients. Besides, the results showed high expressions of CCL2 in the visceral adipose tissue (VAT) and placenta tissue in the GDM mice. Flow cytometry and immunohistochemistry (IHC) staining showed the accumulations of macrophages in these tissues. Treatment of αCCL2 attenuated the GDM symptoms and ameliorated the inflammation. Furthermore, the treatment of αCCL2 improved reproductive outcomes in the GDM mice. Blockade of CCL2 attenuated GDM symptoms and reduced inflammatory cytokines in a genetic mice model.

Decreased Monocyte Count is Associated with Gestational Diabetes Mellitus Development, Macrosomia and Inflammation

2021 ◽  
Author(s):  
Xinmei Huang ◽  
Bingbing Zha ◽  
Manna Zhang ◽  
Yue Li ◽  
Yueyue Wu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cohort Study ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Glucose Level ◽  
First Trimester ◽  
Case Control ◽  
Monocyte Count ◽  
Tnf Α ◽  
Newborn Weight

Abstract Objective The immune system plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). Monocytes, the main innate immune cells, are especially important in the maintenance of a normal pregnancy. Here, we investigated the potential effect of monocytes in GDM. Materials and Methods: Monocyte count was monitored throughout pregnancy in 214 women with GDM and 926 women without in a case-control and cohort study. Circulating levels of inflammatory cytokines, placenta-derived macrophages and their products were measured. Results Throughout pregnancy, monocyte count was significantly decreased in women with GDM, and closely associated with glucose level, insulin resistance and newborn weight. First-trimester monocyte count outperformed that of the second and third trimester as a risk factor and diagnostic predictor of GDM and macrosomia in both the case-control and cohort study. In addition, our cohort study showed that as first-trimester monocyte count decreased, GDM and macrosomia incidence, glucose level and newborn weight increased in a stepwise manner. Risk of GDM started to decrease rapidly when first-trimester monocyte count exceeded 0.48 × 10 9/L. Notably, CD206 and IL-10 were significantly lower, while CD80, CD86, TNF-α and IL-6 were higher in both GDM placental tissue and peripheral blood. First-trimester monocyte count was positively related to IL-10 and CD206, but negatively related to CD80, CD86, TNF-α and IL-6. Conclusions Decreased monocyte count throughout pregnancy was closely-associated with the development of GDM, macrosomia and the chronic inflammatory state of GDM. First-trimester monocyte count has great potential as an early diagnostic marker of GDM.

scholarly journals Oleuropein alleviates gestational diabetes mellitus by activating AMPK signaling

2020 ◽  
Author(s):  
Zhiwei Zhang ◽  
Hui Zhao ◽  
Aixia Wang
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Body Weight ◽  
Blood Glucose ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Signaling Pathway ◽  
Hepatic Glycogen ◽  
Ampk Signaling ◽  
Tnf Α

Background: Gestational diabetes mellitus (GDM) has a high incidence rate among pregnant women. The objective of the study was to assess the effect of plant-derived oleuropein in attenuating inflammatory and oxidative stress of GDM. Methods: Oleuropein was administered to GDM mice at the doses of 5 or 10 mg/kg/day. Body weight, blood glucose, insulin and hepatic glycogen levels were recorded. To evaluate the effect of oleuropein in reducing oxidative stress, enzyme-linked immunosorbent assay (ELISA) was used to measure the hepatic oxidative stress markers. The inflammation levels of GDM mice were evaluated by measuring serum levels of IL-6 and TNF-α by ELISA, and mRNA levels of IL-1β, TNF-α and IL-6 by real-time PCR (RT-PCR). The AMP-activated protein kinase (AMPK) signaling pathway was assessed by Western blot. Gestational outcome was analyzed through comparing litter size and birth weight. Results: Oleuropein attenuated the elevated body weight of GDM mice, and efficiently reduced blood glucose, insulin and hepatic glycogen levels. Oxidative stress and inflammation were alleviated by oleuropein treatment. The AMPK signaling was activated by oleuropein in GDM mice. Gestational outcome was markedly improved by oleuropein treatment. Conclusions: Our study suggests that oleuropein is effective in alleviating symptoms of GDM and improving gestational outcome in the mouse model. This effect is achieved by attenuating oxidative stress and inflammation, which is mediated by the activation of the AMPK signaling pathway.

scholarly journals Expression of Dual-Specificity Phosphatase 9 in Placenta and Its Relationship with Gestational Diabetes Mellitus

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Qiang Wei ◽  
Xiaomin Pu ◽  
Li Zhang ◽  
Yi Xu ◽  
Meifan Duan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Body Mass Index ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Pregnant Women ◽  
Plasma Glucose ◽  
Mrna Levels ◽  
Gestational Week

Introduction. The aim of the present study was to examine placental levels of DUSP9 mRNA and protein and to investigate the potential role of DUSP9 in the development of gestational diabetes mellitus (GDM). Methods. Placental tissues from pregnant women with GDM (n=17) and normal healthy pregnant women (n=16) were collected at delivery. The expression of DUSP9 mRNA in placental tissue was analyzed by real-time PCR, while the expression of DUPS9 protein was evaluated by immunohistochemistry and western blot. Differences in the expression levels of DUSP9 mRNA and protein between the two groups were assessed, as well as potential correlations between DUSP9 mRNA expression levels and relevant clinical indicators. Results. Blood glucose levels were significantly higher in the GDM group than in the control group, based on an oral glucose tolerance test. DUSP9 protein was expressed in the placental cytotrophoblasts in both groups, and placental levels of DUSP9 protein and mRNA were significantly higher in women with GDM. Placental DUSP9 mRNA levels in all 33 women correlated moderately with delivery gestational week (R=0.465, P=0.006), fasting plasma glucose (R=0.350, P=0.046), 1-hour postload plasma glucose (R=0.363, P = 0.038), and 2-hour postload plasma glucose (R=0.366, P=0.036), but not with maternal age, preconception body mass index, prenatal body mass index, or neonatal birth weight. Multiple linear regression analysis indicated that delivery gestational week was an influence factor of DUSP9 mRNA levels (β1=0.026, P<0.05). Conclusions. DUSP9 upregulation in the placenta of GDM pregnant women may promote insulin resistance, which may correlate with the occurrence of GDM. But there is still possibility that DUSP9 upregulation was the results of insulin resistance and/or hyperglycemia. Further research is needed to explore the role of DUSP9 in GDM.

scholarly journals Anti-inflammatory activities of puerarin in high-fat diet-fed rats with streptozotocin-induced gestational diabetes mellitus

2020 ◽  
Vol 47 (10) ◽  
pp. 7537-7546 ◽  
Author(s):  
Wenting Xu ◽  
Mengyu Tang ◽  
Jiahui Wang ◽  
Lihong Wang
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Density Lipoprotein ◽  
Reproductive Organs ◽  
Control Group ◽  
High Fat ◽  
Adipose Tissues ◽  
Tnf Α

Abstract To investigate the effect of puerarin on insulin resistance and inflammation in rats with gestational diabetes mellitus (GDM). Gestational diabetic model rats were established by intraperitoneal injection of streptozotocin (25 mg/kg) combined with high-fat feeding and were randomly assigned to three groups: the control group, the GDM group, and the puerarin-treated group. Puerarin was intragastrically administered to rats daily until the offspring were born. The rats in both the GDM group and control group were administered the same volume of normal saline. Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in all groups of rats were measured. Haematoxylin and eosin staining was used to evaluate morphological changes in the liver, pancreas, and adipose tissues around the reproductive organs. Western blotting was carried out to measure the protein expression of IRS-1 and inflammatory factors, including TNF-α, TLR4, MyD88 and phosphorylated NF-κB, in the adipose tissues around the reproductive organs. Puerarin had preventive effects on GDM-induced pathological changes and ameliorated glucose and lipid metabolism disorders in GDM rats. Puerarin upregulated IRS-1 expression and decreased the protein expression of TNF-α, TLR4, and MyD88 as well as the levels of phosphorylated NF-κB in adipose tissues around the reproductive organs in GDM rats. This study indicated that puerarin exerts anti-inflammatory effects by downregulating the important TLR4/MyD88/NF-κB inflammatory signalling pathway. Therefore, puerarin can decrease the expression of TNF-α and ameliorate insulin resistance in GDM rats, suggesting the potential efficacy of puerarin in GDM treatment.

scholarly journals Inflammatory and Adipokine Status from Early to Midpregnancy in Arab Women and Its Associations with Gestational Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Sara Al-Musharaf ◽  
Shaun Sabico ◽  
Syed Danish Hussain ◽  
Fatima Al-Tawashi ◽  
Haifa Bandar AlWaily ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
International Association ◽  
Multivariate Logistic Regression Analysis ◽  
Arab Women ◽  
Second Trimester ◽  
Markers Of Inflammation ◽  
Tnf Α ◽  
Iadpsg Criteria

Objective. To examine differences in maternal serum levels of adipokines (adiponectin, leptin, and resistin) and inflammatory markers (tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6)) from early to midpregnancy among Arab women with or without gestational diabetes mellitus (GDM), along with their links to GDM risk. Methods. This is a multicenter prospective study involving 232 Saudi women attending obstetric care. Both circulating adipokine and markers of inflammation were observed at the first (eight to 12 weeks) and second trimesters (24 to 28 weeks). GDM was screened at 24 to 28 weeks using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Results. Age and body mass index- (BMI-) matched circulating TNF-α was significantly higher in women with GDM in comparison to non-GDM women ( p = 0.01 ). Adiponectin and resistin significantly decreased from the first to second trimester in women without GDM ( p = 0.002 and 0.026, respectively). Leptin presented a significant rise from the first to second trimester in both groups, with a higher increase in women with GDM ( p = 0.013 ). Multivariate logistic regression analysis revealed that TNF-α was significantly correlated with GDM ( p = 0.03 ). However, significance was lost after adjustments for maternal and lifestyle risk factors (OR 23.58 (0.50 to 1119.98), p = 0.11 ). Conclusion. Inflammatory and adipocytokine profiles are altered in Arab women with GDM, TNF-α in particular. Further studies are needed to establish whether maternal inflammatory and adipocytokine profile influence fetal levels in the same manner.

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