Cinnamon extract (traditional herb) potentiates in vivo insulin-regulated glucose utilization via enhancing insulin signaling in rats

Abstract

Cinnamon has been shown to potentiate the insulin effect through upregulation of the glucose uptake in cultured adipocytes. In the present study, we evaluated the effect of the cinnamon extract on the insulin action in awaked rats by the euglycemic clamp and further analyzed possible changes in insulin signaling occurred in skeletal muscle. The rats were divided into saline and cinnamon extract (30 and 300 mg/kg BW-doses: C30 and C300) oral administration groups. After 3-weeks, cinnamon extract treated rats showed a significantly higher glucose infusion rate (GIR) at 3 mU/kg per min insulin infusions compared with controls (118 and 146% of controls for C30 and C300, respectively). At 30 mU/kg per min insulin infusions, the GIR in C300 rats was increased 17% over controls. There were no significant differences in insulin receptor (IR)-β, IR substrate (IRS)-1, and phosphatidylinositol (PI) 3-kinase protein content between C300 rats and controls. However, the skeletal muscle insulin-stimulated IR-β and the IRS-1 tyrosine phosphorylation levels in C300 rats were 18 and 33% higher, respectively, added to 41% higher IRS-1/PI 3-kinase association. These results suggest that the cinnamon extract would improve insulin action via increasing glucose uptake in vivo, at least in part through enhancing the insulin-signaling pathway in skeletal muscle.

Introduction

The cinnamon, also known by Cassia, Sweet Wood, and Gui Zhi, is traditionally harvested in Asian countries. It is, perhaps, one of the oldest herbal medicines, having been mentioned in Chinese texts as long as 4000 years ago [1], [2]. The large number of applications for cinnamon indicates the widespread appreciation that folk herbalists around the world have had for cinnamon as a medicine [2], including the treatment of diarrhea, arthritis, etc. [1]. Furthermore, it has been reported that the cinnamon extract has vasodilative, anti-thrombotic, antispastic, anti-ulcerous, and anti-allergic action [2]. In the last decade, in vitro studies revealed that the cinnamon extract mimics the effect of insulin, which potentiates insulin action in isolated adipocytes [3], [4], [5], [6]. It is believed that the methylhydroxychalcone polymer (MHCP, extracted from cinnamon) is responsible for the above effect. MHCP may be useful in the treatment of insulin resistance via increasing glucose utilization in cells [6]. Moreover, the cinnamon extract has also been shown to improve the insulin receptor function [5], [6]. However, to our knowledge, up till now the effect of the cinnamon extract on insulin action has not been demonstrated in in vivo studies.

Insulin resistance is a progressive metabolic disorder characterized by reduced glucose uptake in response to normal concentrations of insulin and is most likely the result of a combination of polygenic defects and environmental factors [7], [8], [9]. The resistance to the action of insulin can result from a variety of causes, including defects both in the receptor binding and at the postreceptor levels [10]. Goodyear et al. [11] and Bjornholm et al. [12] demonstrated that significantly less insulin stimulation of its receptor and IRS-1 tyrosine phosphorylation, as well as IRS-1-immunoprecipitable PI 3-kinase activity, is detected in skeletal muscle from insulin-resistant subjects compared with controls. To evaluate this hypothesis, in the present study, we first determined whether insulin action was really improved by the cinnamon extract administration to Wistar rats by the euglycemic clamp technique. Secondly, as the skeletal muscle is the principal tissue responsible for the insulin-stimulated glucose disposal [13] and the major site of peripheral insulin resistance [14], and due to previous reports that the cinnamon extract affects elements of the PI 3-kinase upstream and activates the insulin receptor kinase [5], we further analyzed whether the cinnamon extract could enhance insulin signaling in skeletal muscle harvested from the experimental animals.