Activation of Insulin Signaling by Botanical Products.

Tovit Rosenzweig,Sanford R Sampson

doi:10.3390/ijms22084193

Abstract

Type 2 diabetes (T2D) is a worldwide health problem, ranked as one of the leading causes for severe morbidity and premature mortality in modern society. Management of blood glucose is of major importance in order to limit the severe outcomes of the disease. However, despite the impressive success in the development of new antidiabetic drugs, almost no progress has been achieved with regard to the development of novel insulin-sensitizing agents. As insulin resistance is the most eminent factor in the patho-etiology of T2D, it is not surprising that an alarming number of patients still fail to meet glycemic goals. Owing to its wealth of chemical structures, the plant kingdom is considered as an inventory of compounds exerting various bioactivities, which might be used as a basis for the development of novel medications for various pathologies. Antidiabetic activity is found in over 400 plant species, and is attributable to varying mechanisms of action. Nevertheless, relatively limited evidence exists regarding phytochemicals directly activating insulin signaling, which is the focus of this review. Here, we will list plants and phytochemicals that have been found to improve insulin sensitivity by activation of the insulin signaling cascade, and will describe the active constituents and their mechanism of action.

Highlights

Type 2 diabetes (T2D) is a chronic progressive disease which develops, in part, as a result of insulin resistance
In addition to the benefit that may be derived from the adoption of a healthy lifestyle to prevent the development or lower the severity of T2D, numerous noninsulin-like antidiabetic drugs have been approved for clinical use
By activating the phosphoinositide 3-kinase (PI3K)-Akt pathway, Grape-seed procyanidins extract (GSPE) appears to exert cardio-protection effects in mice [47] and may be effective in the attenuation of various complications of the disease [48,49]. These outcomes, are considered to be associated with the antioxidative and anti-inflammatory properties of GSPE, rather than with its insulinomimetic effects [50]. Another potential activator of insulin signaling through a direct action on insulin receptors (IR) is ursolic acid (UA), a pentacyclic triterpenoid isolated from Campsis grandiflora (Figure 1D)

Summary

Introduction

Type 2 diabetes (T2D) is a chronic progressive disease which develops, in part, as a result of insulin resistance. In addition to the benefit that may be derived from the adoption of a healthy lifestyle to prevent the development or lower the severity of T2D, numerous noninsulin-like antidiabetic drugs have been approved for clinical use These include drugs developed to fight hyperglycemia by interfering in the various events affecting blood glucose, such as insulin secretagogue (sulfonylureas) [2], glucagon-like peptide 1 (GLP-1) analogues, GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase 4 (DPP-4), the GLP-1 inactivating enzyme. Improved insulin sensitivity following treatment with a particular plant or phytochemical in animal studies does not allow for differentiation between direct insulin-sensitizing activity and indirect effects through the ablation of factors such as inflammation and oxidative stress that promote insulin resistance. Downstream components of the signal are dephosphorylated by lipid phosphatases (PTEN and SHIP2) and serine-threonine phosphatases (PP2A and PHLPP) that antagonize the phosphorylation of phosphatidylinositol-3 phosphate (PIP3) and Akt, respectively [20]

Insulin Receptor Activation by Botanical Compounds

Inhibition of Phosphatases for the Activation of Insulin Signaling

PTP1B Inhibition by Botanical Compounds

Inhibition of Other Phosphatases by Botanical Products

GLUT4 Translocation

Summary and Conclusions