Effect of miR-29b on rats with gestational diabetes mellitus by targeting PI3K/Akt signal.

OBJECTIVE To investigate the role of micro-ribonucleic acid-29b (miR-29b) in rats with gestational diabetes mellitus (GDM) through the phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (Akt) signal and its mechanism by establishing rat models of GDM. MATERIALS AND METHODS Rat models of GDM were constructed, and then the expression levels of miR-29b, total PI3K, phosphorylated PI3K (p-PI3K), total Akt and phosphorylated Akt (p-Akt) in the model group and control group were measured via Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting assays, and the association between miR-29b expression and total PI3K expression was analyzed. In addition, miR-29b mimics and inhibitors were used to further explore the regulatory pathway, and the influences of miR-29b mimics and inhibitors on PI3K and Akt phosphorylation in GDM rats, characteristic indicators of oxidative stress such as superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in liver tissues of GDM rats, and fasting blood glucose in GDM rats were studied. RESULTS Compared with those in the control group, miR-29b expression was lowered in rat models of GDM, while PI3K/Akt signal expression was increased. In rats with GDM, miR-29b expression was prominently negatively correlated with total PI3K expression (r=-0.777, p=0.007, p<0.01). MiR-29b mimics could reduce PI3K and Akt phosphorylation, increase SOD and CAT expression levels and decrease MDA content (p<0.05). Moreover, miR-29b mimics significantly lowered the blood glucose level in rats with GDM (p<0.05). CONCLUSIONS MiR-29b mimics can alleviate oxidative stress and reduce blood glucose by inhibiting the PI3K/Akt signal transduction.

[1]  J. Eriksson,et al.  Gestational hypertension is associated with increased risk of type 2 diabetes in adult offspring: the Helsinki Birth Cohort Study , 2017, American journal of obstetrics and gynecology.

[2]  Xiaodong Zhou,et al.  MicroRNA-29b Inhibits Angiogenesis by Targeting VEGFA through the MAPK/ERK and PI3K/Akt Signaling Pathways in Endometrial Carcinoma , 2017, Cellular Physiology and Biochemistry.

[3]  Yudan Wei,et al.  Changes in Serum Adiponectin in Mice Chronically Exposed to Inorganic Arsenic in Drinking Water , 2017, Biological Trace Element Research.

[4]  N. Guo,et al.  Phytosterol nutritional supplement improves pregnancy and neonatal complications of gestational diabetes mellitus in a double-blind and placebo-controlled clinical study. , 2017, Food & function.

[5]  D. Fornes,et al.  Intrauterine programming of lipid metabolic alterations in the heart of the offspring of diabetic rats is prevented by maternal diets enriched in olive oil. , 2015, Molecular nutrition & food research.

[6]  L. Hou,et al.  GDM Women’s Pre-Pregnancy Overweight/Obesity and Gestational Weight Gain on Offspring Overweight Status , 2015, PloS one.

[7]  Peter Arner,et al.  MicroRNA regulatory networks in human adipose tissue and obesity , 2015, Nature Reviews Endocrinology.

[8]  A. Jawerbaum,et al.  PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats. , 2014, Journal of molecular endocrinology.

[9]  R. Poulsom,et al.  In Crohn's disease fibrosis-reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts. , 2014, Clinical science.

[10]  T. Haaf,et al.  Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment , 2014, Reproduction.

[11]  Young Seol Kim,et al.  Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance , 2013, The Korean journal of internal medicine.

[12]  J. Kern,et al.  Prevalence and five-year cumulative incidence of abdominal obesity in Croatian women of childbearing age: the CroHort study. , 2012, Collegium Antropologicum.

[13]  A. Jawerbaum,et al.  Animal models in diabetes and pregnancy. , 2010, Endocrine reviews.

[14]  S. Bronk,et al.  Transcriptional suppression of mir‐29b‐1/mir‐29a promoter by c‐Myc, hedgehog, and NF‐kappaB , 2010, Journal of cellular biochemistry.

[15]  Yi Tan,et al.  Oxidative Stress, Diabetes, and Diabetic Complications , 2009, Hemoglobin.

[16]  S. R. Kulkarni,et al.  Characteristics of gestational diabetic mothers and their babies in an Indian diabetes clinic. , 2005, The Journal of the Association of Physicians of India.

[17]  D. Trisciuoglio,et al.  Involvement of PI3K and MAPK signaling in bcl-2-induced vascular endothelial growth factor expression in melanoma cells. , 2005, Molecular biology of the cell.

[18]  M. Plebani,et al.  Lymphocyte subsets and cytokines in women with gestational diabetes mellitus and their newborn. , 2005, Cytokine.

[19]  M. Eskandar,et al.  Complications of pregnancy and foetal outcomes in pregnant diabetic patients managed in a tertiary hospital in Saudi Arabia. , 2005, West African journal of medicine.

[20]  M. Katz,et al.  Gestational diabetes complicated by hydramnios was not associated with increased risk of perinatal morbidity and mortality. , 2001, European journal of obstetrics, gynecology, and reproductive biology.

[21]  J. Friedman,et al.  Impaired glucose transport and insulin receptor tyrosine phosphorylation in skeletal muscle from obese women with gestational diabetes. , 1999, Diabetes.

[22]  B. Metzger,et al.  Increased Macrosomia and Perinatal Morbidity Independent of Maternal Obesity and Advanced Age in Korean Women With GDM , 1997, Diabetes Care.

[23]  Y-L Chen,et al.  Regulation of DNA methylation and tumor suppression gene expression by miR-29b in leukemia patients and related mechanisms. , 2018, European review for medical and pharmacological sciences.

[24]  N. Munshi,et al.  miR-29 b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp , 2012 .

[25]  P. Patil,et al.  Use of natural antioxidants to scavenge free radicals: a major cause of diseases. , 2010 .