The potential effect of polyphenols in emerging pharmacological liver targets for glucose regulation and insulin resistance: a review

Abstract

In type 2 diabetes mellitus (DM), there is a combination of impaired insulin secretion and resistance in the target tissues. In the case of the liver, these events lead to decreased insulin effectiveness and increased glucagon levels, resulting in an imbalance that promotes excessive hepatic gluconeogenesis and glycogenolysis, contributing to hyperglycemia. Effective management of hyperglycemia and insulin resistance is crucial, underscoring the need for innovative liver-specific interventions. Polyphenols, renowned for their diverse biological activities, have emerged as promising candidates to treat type 2 DM. Based on a literature review spanning the last decade, this comprehensive systematic review thoroughly evaluates the effectiveness of polyphenols in targeting hepatic pathways for managing type 2 DM. The focus will be on assessing how polyphenols affect key targets, including protein tyrosine phosphatase 1B (PTP1B), the glucagon receptor, glucokinase, glycogen phosphorylase, and fructose 1,6-bisphosphatase. While there has been considerable attention on polyphenols as PTP1B inhibitors, studies on their impact on other targets have been comparatively limited. Notably, there is a lack of studies exploring polyphenols as glucagon receptor antagonists. Among polyphenols, flavonoids exhibit significant potential across diverse pathways, with hydroxy groups playing a pivotal role in their biological activities. However, further research, especially in cellular and animal models, is warranted to thoroughly validate their efficacy.