scholarly journals miR-410 enhanced hESC-derived pancreatic endoderm transplant to alleviate gestational diabetes mellitus

2015 ◽  
Vol 55 (3) ◽  
pp. 219-229 ◽  
Author(s):  
Yang Mi ◽  
Na Guo ◽  
Tongqiang He ◽  
Jing Ji ◽  
Zhibin Li ◽  
...  

Gestational diabetes mellitus (GDM) is a condition commonly encountered during mid to late pregnancy with pathologic manifestations including hyperglycemia, hyperinsulinemia, insulin resistance, and fetal mal-development. The deficit and dysfunction of insulin secreting β-cells are signature symptoms for GDM. Pancreatic progenitors derived from human embryonic stem cells (hESCs) were shown to be able to effectively treat diabetes in mice. In this study, we first identified that microRNA-410 (miR-410) directly targets lactate dehydrogenase A (LDHA), a gene selectively repressed in normal insulin secreting β-cells. hESCs that can be induced to express miR-410 hence keeping LDHA levels in check were then differentiatedin vitrointo pancreatic endoderm, followed by transplantation intodb/+mouse model of GDM. The transplant greatly improved glucose metabolism and reproductive outcome of the pregnant females suffering from GDM. Our findings describe for the first time the method of combining miRNA with hESCs, providing proof of concept by employing genetically modified stem cell therapy for treating GDM.

2021 ◽  
Author(s):  
Haowen Zhang ◽  
Ce Qi ◽  
Yuning Zhao ◽  
Mengyao Lu ◽  
Xinyue Li ◽  
...  

Gestational diabetes mellitus (GDM) may be related to intestinal mucosal damage and inflammation-induced dysbiosis of secretory IgA (SIgA) coated microbiota. SIgA coated L. reuteri can reduce the level of inflammation of GDM in vitro.


2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Pingping Wang ◽  
Zengfang Wang ◽  
Guojie Liu ◽  
Chengwen Jin ◽  
Quan Zhang ◽  
...  

MicroRNA (miRNA) has been widely suggested to play a vital role of in the pathogenesis of gestational diabetes mellitus (GDM). We have previously demonstrated that miR-657 can regulate macrophage inflammatory response in GDM. However, the role of miR-657 on M1/M2 macrophage polarization in GDM pathogenesis is not clear yet. This study is aimed at elucidating this issue and identifying novel potential GDM therapeutic targets based on miRNA network. miR-657 is found to be upregulated in placental macrophages demonstrated by real-time PCR, which can enhance macrophage proliferation and migration in vitro. Luciferase reporter assay shows the evidence that FAM46C is a target of miR-657. In addition, miR-657 can promote macrophage polarization toward the M1 phenotype by downregulating FAM46C in macrophages. The present study strongly suggests miR-657 is involved in GDM pathogenesis by regulating macrophage proliferation, migration, and polarization via targeting FAM46C. miR-657/FAM46C may serve as promising targets for GDM diagnosis and treatment.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xuegui Zhou ◽  
Cuiping Xiang ◽  
Xiaoxia Zheng

Abstract Background Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes. Strategies that improve trophoblast cell function are important methods for GDM treatment. This study aimed to investigate the expression and diagnostic potential of microRNA-132 (miR-132) in GDM patients, and further analyzed the effects of miR-132 on HTR-8/SVneo cell proliferation. Methods Quantitative real-time PCR was applied to estimate the expression of miR-132. A receiver operating characteristics curve (ROC) analysis was performed to evaluate the diagnostic value of serum miR-132 in GDM patients. In vitro regulation of miR-132 in trophoblast cell HTR-8/SVneo was achieved by cell transfection, and the effects of miR-132 on cell proliferation were assessed using CCK-8 assay. Results Expression of miR-132 was decreased in serum and placenta tissues in GDM patients compared with the healthy women. A negative correlation was found between the serum miR-132 levels and fasting blood glucose of the GDM patients. A ROC curve shown the serum miR-132 had considerable diagnostic accuracy with an area under the curve (AUC) of 0.898. High glucose (HG) treatment induced an inhibition in HTR-8/SVneo cell proliferation and the expression of miR-132. The overexpression of miR-132 in HTR-8/SVneo cells could markedly rescued the HG - induced suppressed cell proliferation. Conclusion All the data of this study revealed the reduced expression of miR-132 in serum and placenta tissues of GDM, and serum miR-132 serves a candidate biomarker in the diagnosis of GDM. miR-132 may act a protective role against GDM via enhancing the trophoblast cell proliferation.


2015 ◽  
Vol 4 (3) ◽  
pp. 487-491
Author(s):  
Daniela Callegari ◽  
Carla Bresciani ◽  
Ezio Bianchi ◽  
Valeria De Cesaris ◽  
Enrico Parmigiani ◽  
...  

Gestational diabetes mellitus (GDM) is a rare disease in dogs that depends from an endogenous insulin supply that is insufficient to meet the tissues demands for the action of diabetogenic molecules like progesterone (P4), estradiol, growth hormone (GH), placental lactogen and placental cytokines. This report describes for the first time a case of GDM complicated by ketoacidosis treated with the P4 receptor blocker aglepristone. In our case aglepristone seemed to increase insulin sensitivity, helping in the resolution of ketoacidosis and of diabetes mellitus. Aglepristone may represent an effective and well tolerated therapeutic option in case of GDM.


Author(s):  
В. В. Боброва

Цукровий діабет є досить поширеним захворюванням серед людей та тварин. На сьогодні ветеринарні клініцисти відмічають певне збільшення кількості собак та котів, яким встановлено діагноз «цукровий діабет». Окрему проблему на лікувальному етапі  становить контроль над рівнем глюкози за наявності резистентності тканин організму до інсуліну. У роботі наведено аналіз клінічного випадку інсулінорезистентності за гестаційного діабету у не стерилізованої суки. Diabetes mellitus is a fairly common disease among humans and animals. Today veterinarians mark a certain increase in the number of dogs and cats diagnosed with diabetes mellitus. It is a hormonal disease characterized by the presence of hyperglycemia and permanent glucosuria. The causes of diabetes are absolute or relative insufficiency of insulin synthesis by the pancreas (first type or insulin dependent diabetes, more common in dogs) and insulin resistance of the body with β-cell dysfunction (second type or non-insulin dependent diabetes, more commonly sick of cats). Permanent degeneration of β-cells occurs due to enhanced insulin synthesis. Treatment in the first and second cases is carried out by insulin. In animals with diabetes, polydipsia/polyuria syndrome is manifest, may be complications in the form of ketoacidosis, which is characterized by significant violations of acid-alkaline and electrolyte balances, which directly endangers life. Separate secretion of secondary or transient diabetes, which occurs due to the development of another disease – pancreatitis, hyperadrenocorticism or long-term use of progestogens and glucocorticoids. Timely detection and treatment of the primary disease with the neutralization of the causes of hyperglycemia to the desolation of β-cells can lead to recovery. It also applies to gestational diabetes mellitus, which may occur during the late pregnancy or diestrus in a female dog, when high levels of progesterone, somatotropin and structurally similar hormones cause the appearance of insulin resistance of the tissues of the body. Timely control of hyperglycemia and subsequent ovariogestarter­ectomy contributes to the recovery of the animal. Unfortunately, the issue of controlling hyperglycemia in the occurrence of insulin resistance in the treatment of diabetes is very complicated and does not provide immediate results. The paper presents an analysis of the clinical case of insulin resistance in gestational diabetes in a non-sterilized female dog.


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