Antidiabetic Activities of Abutilon indicum (L.) Sweet Are Mediated by Enhancement of Adipocyte Differentiation and Activation of the GLUT1 Promoter

Chutwadee Krisanapun,Seung Joon Baek,Penchom Peungvicha,Rungravi Temsiririrkkul,Seong-Ho Lee

doi:10.1093/ecam/neq004

Abstract

Abutilon indicum (L.) Sweet is an Asian phytomedicine traditionally used to treat several disorders, including diabetes mellitus. However, molecular mechanisms supporting the antidiabetic effect of A. indicum L. remain unknown. The aim of this study was to evaluate whether extract of A. indicum L. improves insulin sensitivity. First, we observed the antidiabetic activity of aqueous extract of the entire plant (leaves, twigs and roots) of A. indicum L. on postprandial plasma glucose in diabetic rats. The subsequent experiments revealed that butanol fractions of the extract bind to PPARγ and activate 3T3-L1 differentiation. To measure glucose uptake enhanced by insulin-like activity, we used rat diaphragm incubated with various concentrations of the crude extract and found that the extract enhances glucose consumption in the incubated solution. Our data also indicate that the crude extract and the fractions (water and butanol) did not affect the activity of kinases involved in Akt and GSK-3β pathways; however, the reporter assay showed that the crude extract could activate glucose transporter 1 (GLUT1) promoter activity. These results suggest that the extract from A. indicum L. may be beneficial for reducing insulin resistance through its potency in regulating adipocyte differentiation through PPARγ agonist activity, and increasing glucose utilization via GLUT1.

Highlights

Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both; the incidence of diabetes is increasing worldwide
Our data indicate that the crude extract and the fractions did not affect the activity of kinases involved in Akt and GSK-3β pathways; the reporter assay showed that the crude extract could activate glucose transporter 1 (GLUT1) promoter activity
These results suggest that the extract from A. indicum L. may be beneficial for reducing insulin resistance through its potency in regulating adipocyte differentiation through PPARγ agonist activity, and increasing glucose utilization via GLUT1

Summary

Introduction

Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both; the incidence of diabetes is increasing worldwide. Diabetes or obesity causes substantial morbidity, mortality and long-term complications, and remains an important risk factor for cardiovascular disease [1]. Insulin resistance is a key feature in type 2 DM as well as in obesity and plays an important pathophysiological role [3]. Impairment of insulin action has been observed in syndromes including inflammatory and chronic infectious diseases in addition to type 2 DM [4]. Recent data suggest that activation of PPARγ by using plant extracts improves lipid metabolism and mitigates insulin resistance [5]. Traditional antidiabetic plants possess less adequate scientific or medicinal data support in spite of the fact that the World Health Organization still recommends further evaluation of their accepted use [8, 9]

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