Marine Bromophenol Derivative 3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-isopropoxymethyl benzyl)benzene-1,2-diol Protects Hepatocytes from Lipid-Induced Cell Damage and Insulin Resistance via PTP1B Inhibition.

Jiao Luo,Lijun Wang,Changhui Wang,Bo Jiang,Baocheng Wang,Xiangqian Li,Ning Wu,Dayong Shi,Shuaiyu Wang

doi:10.3390/md13074452

Abstract

3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-isopropoxymethyl benzyl)benzene-1,2-diol (HPN) is a bromophenol derivative from the marine red alga Rhodomela confervoides. We have previously found that HPN exerted an anti-hyperglycemic property in db/db mouse model. In the present study, we found that HPN could protect HepG2 cells against palmitate (PA)-induced cell death. Data also showed that HPN inhibited cell death mainly by blocking the cell apoptosis. Further studies demonstrated that HPN (especially at 1.0 μM) significantly restored insulin-stimulated tyrosine phosphorylation of IR and IRS1/2, and inhibited the PTP1B expression level in HepG2 cells. Furthermore, the expression of Akt was activated by HPN, and glucose uptake was significantly increased in PA-treated HepG2 cells. Our results suggest that HPN could protect hepatocytes from lipid-induced cell damage and insulin resistance via PTP1B inhibition. Thus, HPN can be considered to have potential for the development of anti-diabetic agent that could protect both hepatic cell mass and function.

Highlights

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder resulting in insulin resistance of the peripheral tissues and impaired insulin secretion from the pancreas [1,2]
This study explores the role of HPN in insulin resistance induced by PA and the possible molecular mechanisms underlying PA-induced cell damage and insulin resistance in HepG2 cells
The results suggest that HPN has no significant growth-inhibiting or growth-promoting effect on HepG2 cells

Summary

Introduction

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder resulting in insulin resistance of the peripheral tissues and impaired insulin secretion from the pancreas [1,2]. Several specific molecular targets in the insulin signaling pathway have been considered as novel therapeutic approaches for type 2 diabetes [3,4]. The insulin signaling is initiated when insulin binds to insulin receptor (IR) which results in IR auto-phosphorylation of key tyrosine residues [5]. Tyrosine residues of insulin receptor substrate (IRS) are subsequently phosphorylated by the IR kinase which can further trigger downstream. Activated Akt plays a pivotal role in the glucose metabolism which can activate insulin-stimulated glucose transport and regulates glycogen synthesis by GSK-3α and β inactivation [6]. Phosphorylated Akt signaling cascades have a critical role in cell survival and apoptosis regulation

Results

Discussion

Conclusion