Abstract

Insulin resistance (IR) plays a central role in the development of several metabolic diseases, which leads to increased morbidity and mortality rates, in addition to soaring health-care costs. Deep sea water (DSW) and fucoidans (FPS) have drawn much attention in recent years because of their potential medical and pharmaceutical applications. This study investigated the effects and mechanisms of combination treatment of DSW and FPS in improving IR in HepG2 hepatocytes induced by a high glucose concentration. The results elucidated that co-treatment with DSW and FPS could synergistically repress hepatic glucose production and increase the glycogen level in IR-HepG2 cells. In addition, they stimulated the phosphorylation levels of the components of the insulin signaling pathway, including tyrosine phosphorylation of IRS-1, and serine phosphorylation of Akt and GSK-3β. Furthermore, they increased the phosphorylation of AMPK and ACC, which in turn decreased the intracellular triglyceride level. Taken together, these results suggested that co-treatment with DSW and FPS had a greater improving effect than DSW or FPS alone on IR. They might attenuate IR by targeting Akt/GSK-3β and AMPK pathways. These results may have some implications in the treatment of metabolic diseases.

Highlights

  • Changes in life styles and eating habits have resulted in so-called lifestyle-related illnesses such as hyperlipidemia, hypertension, and diabetes, leading to increased morbidity and mortality rates and a social burden worldwide

  • The results suggested that co-treatment at different hepatic glucose production and enhanced with glycogen synthesis in insulin resistance (IR)-HepG2 cells.concentrations

  • The results indicated that the inhibition of AMPK and ACC phosphorylation in cells exposed to high glucose concentrations was synergistically restored by co-treatment with Deep sea water (DSW) and FPS, which was consistent with a decreasing intracellular triglyceride level

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Summary

Introduction

Changes in life styles and eating habits have resulted in so-called lifestyle-related illnesses such as hyperlipidemia, hypertension, and diabetes, leading to increased morbidity and mortality rates and a social burden worldwide. Most of these diseases are characterized by one distinct defect: insulin resistance (IR) [1]. The liver is an insulin sensitive organ that plays a key role in the regulation of whole body energy homeostasis, and hepatic IR immensely increases the risk of impaired fasting glucose and type 2 diabetes [2]. The high glucose condition causes a significant increase of the serine (Ser)

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