Abstract
Methylation of hypoxia-inducible factor-3α (HIF3A) was previously demonstrated to be highly associated with insulin resistance (IR) in patients with gestational diabetes mellitus (GDM). We aimed to study the therapeutic effects of Berberine (BBR) on GDM and the possible mechanisms. The expressions and methylated states of HIF3A in pregnant women with GDM were compared with that in healthy controls. The IR cell models of 3T3-L1 adipocytes was constructed by 1 μmol/l dexamethasone (Dex) and 1 μmol/l insulin (Ins). To evaluate the effects of BBR on IR adipocyte models, cells were subjected to BBR treatment at different concentrations. Transfection of HIF3A siRNA further confirmed the role of HIF3A in the BBR-induced improving effects. Low expression and high methylation of HIF3A gene were frequent in the GDM pregnancies. BBR treatment noticeably increased the glucose usage rates, adiponectin secretion and cell differentiation of IR 3T3-L1 adipocytes. Increased HIF3A expression and decreased methylated state of HIF3A were also found in IR adipocytes. Furthermore, HIF3A silencing not only reversed the effects of BBR on improving insulin sensibility, but also partially abolished the expression alterations of insulin-related genes in IR adipocytes induced by BBR treatment. Our results suggest that BBR improves insulin sensibility in IR adipocyte models, and the improving effects of BBR are possibly realized through the inhibition of HIF3A methylation.
Highlights
As a common medical complication in pregnancy, gestational diabetes mellitus (GDM) is defined as hyperglycemia caused by glucose intolerance and is first detected during pregnancy
We compared the mRNA levels of hypoxia-inducible factor-3α (HIF3A) in the subcutaneous adipose tissues between the GDM and healthy pregnant women, and found that low-expressed HIF3A was common in the GDM group, compared with that in the normal group (Figure 1A)
Our results indicated that BBR showed a potently improving ability in the insulin sensibility of insulin resistance (IR) adipocyte models, and such effects of BBR on IR model may rely on the reduction in HIF3A methylation and the increased expression of HIF3A
Summary
As a common medical complication in pregnancy, gestational diabetes mellitus (GDM) is defined as hyperglycemia caused by glucose intolerance and is first detected during pregnancy. For pregnant women with GDM, they were at a high risk of developing eclampsia, hypertension of pregnancy, placental abruption and/or other obstetric complications [4]. The intrauterine high-glucose environment in GDM pregnancy severely affects the development of the fetus and could cause fetal malformation, macrosomia or other adverse pregnancy outcomes [7]. These babies were more likely to develop type II diabetes, childhood obesity or metabolic syndrome [8]. As GDM greatly affects the health of both pregnant women and their fetuses, identifying safe and effective therapeutic methods has become a focus of public health [9]
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