Cinnamon extract and polyphenols affect the expression of tristetraprolin, insulin receptor, and glucose transporter 4 in mouse 3T3-L1 adipocytes

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Abstract

Cinnamon improves glucose and lipid profiles of people with type 2 diabetes. Water-soluble cinnamon extract (CE) and HPLC-purified cinnamon polyphenols (CP) with doubly linked procyanidin type-A polymers display insulin-like activity. The objective of this study was to investigate the effects of cinnamon on the protein and mRNA levels of insulin receptor (IR), glucose transporter 4 (GLUT4), and tristetraprolin (TTP/ZFP36) in mouse 3T3-L1 adipocytes. Immunoblotting showed that CP increased IRβ levels and that both CE and CP increased GLUT4 and TTP levels in the adipocytes. Quantitative real-time PCR indicated that CE (100 μg/ml) rapidly increased TTP mRNA levels by approximately 6-fold in the adipocytes. CE at higher concentrations decreased IRβ protein and IR mRNA levels, and its effect on GLUT4 mRNA levels exhibited a biphasic pattern in the adipocytes. These results suggest that cinnamon exhibits the potential to increase the amount of proteins involved in insulin signaling, glucose transport, and anti-inflammatory/anti-angiogenesis response.

Section snippets

Cinnamon extract and polyphenols

Water-soluble CE was prepared as described previously [8] with modifications. Briefly, ground cinnamon (Cinnamomum burmannii) was suspended in 0.1 N acetic acid. The suspension was autoclaved for 15 min at 15 psi and the supernatant was mixed with four volumes of absolute ethanol and refrigerated overnight. The mixture was filtered through glass wool and then Whatman No. 1 filter paper. The ethanol was removed by rotoevaporation and the remaining solution was freeze-dried. The dried CE was

Effect of cinnamon extract and polyphenols on the protein levels of insulin receptor β

We first examined the steady state levels of IRβ following initial serum starvation using IRβ-specific antibodies. Immunoblotting showed that IRβ protein levels were similar in adipocytes harvested in all of the time points tested, from 30 min to 3 h beyond the initial serum starvation, as well as the controls using 0.01–1% of DMSO treatments (data not shown), suggesting that the amount of IRβ protein was quite constant in mouse 3T3-L1 adipocytes under these experimental conditions.

Discussion

Plants have been used for the treatment of diabetes since 1550 BC [2]. In search for plant products for diabetic prevention and cure, we and others have shown that common spices (cinnamon, cloves, turmeric, and bay leaves) and tea display insulin-like activity in vitro. We have demonstrated that cinnamon improves glucose and lipid profiles of people with type 2 diabetes [15], and that cinnamon exhibits insulin-like activity in cells, animals and people with type 2 diabetes [8], [9], [10], [11],

Acknowledgments

We greatly appreciate Dr. Perry J. Blackshear (NIH/NIEHS) for his generous support of the experiments related to TTP and Dr. Harry Dawson for designing the IR and GLUT4 primers and probes. We also thank Meghan Kelly and Noella Bryden for technical assistance, Drs. Joseph Urban, Norberta Schoene, John Striffler, and Allen Smith for valuable discussions and helpful comments on the manuscript. This work was supported in part by USDA-ARS Human Nutrition Research Program and PhytoMedical

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