Mechanism of pomegranate ellagic polyphenols reducing insulin resistance on gestational diabetes mellitus rats

Am J Transl Res. 2019 Sep 15;11(9):5487-5500. eCollection 2019.

Abstract

Background: Pomegranate ellagic polyphenols (PEP) has been used as a good medicine in many cultures throughout history. However, the mechanism of PEP regulated insulin resistance on gestational diabetes mellitus (GDM) rats is unclear. The main purpose of the present study was to explore the efficacy and mechanisms of PEP regulated in GDM rats.

Materials and methods: Then, ELISA assay indicated that the levels of serum RBP4, Hcy, GA and FFA were lower in PEP groups than GDM groups in a dose-dependent manner. TUNEL staining showed that PEP improved the pathological changes and inhibited the cell apoptosis in the pancreatic and placenta tissues, respectively.

Results: We found that PEP improved the weight of pregnant rats and fetal rats and the level of blood glucose, blood biochemical index, insulin resistance in GDM rats. Results from H&E and immunohistochemical analysis found that PEP decreased the expressions of APN and Chemerin. Further, PEP decreased the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP), and increased the levels of 11β-hydroxy steroid dehydrogenase type 2 (11β-HSD2) and PPARα-TRB3-AKT2-p-FOXO1-GLUT2 signal related to insulin sensitivity in a dose-dependent manner.

Conclusions: In conclusion, we have demonstrated that PEP may be a candidate drug for the treatment of GDM and guide the clinical therapy.

Keywords: 11β-HSD2; GLUT2; PPARα; Pomegranate ellagic polyphenols; gestational diabetes mellitus; insulin resistance.