Anti–diabetic effects of cinnamaldehyde and its molecular mechanisms

Abstract

Objective To evaluate the effect of cinnamaldehyde (Cin) on glucose and lipids profiles in rats with type 2 diabetes mellitus (T2DM), subsequently to investigate its molecular mechanisms for reducing insulin resistance (IR). Methods Rat models of T2DM were established by combination of high–fat diet induction and intraperitoneal injection of low–dose streptozotocin. Rats were divided into the normal control group (NC), T2DM group, T2DM+ metformin (Met) group and T2DM + Cin group. After four weeks of treatment, blood was extracted for measurement of serum glucose, insulin and lipids. Western blot was used to detect the serum or tissue retinol–binding–protein 4(RBP4) and glucose transporter 4(GLUT4) protein levels. Immunohistochemistry was applied to detect the expression of insulin receptor substrate–1 (IRS–1) and phosphatidylinositol 3–kinase (PI3K) regulatory subunit p85 alpha (p85α) in gastrocnemius muscles. Results Cin displayed promising hypolipidemic, anti–hyperglycemic, and insulin sensitizing functions (FPG: (7.5±1.5) vs (22.7±4.0) mmol/L; TG: (0.77±0.15) vs(1.53±0.13)mmol/L; HOMA–IR: 8.0±3.0 vs 61.2±12.1, P<0.01) compared with the T2DM group. Serum RBP4 levels in Cin treated rats were markedly lowered, and the protein contents of tissue GLUT4 were significantly up–regulated. Also, Cin increased the expression of IRS–1 in gastrocnemius muscles of T2DM rats (0.52±0.05 vs 0.63±0.06, P<0.05), whereas notably decreased the expression of p85α (0.51±0.05 vs 0.43±0.04, P<0.05). Conclusion Cinnamaldehyde can improve glucose and lipids metabolism in type 2 diabetic rats and its pharmacological mechanisms are at least partially related with reducing serum RBP4 concentration, increasing IRS–1 and decreasing of p85α in gastrocnemius muscles. Key words: Cinnamaldehyde; Type 2 diabetes mellitus; Retinol binding protein 4; Phosphatidylinositol 3–kinase regulatory subunit p85α; Insulin receptor substrate–1