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Open AccessArticle

Protective Effects of Gomisin N against Hepatic Cannabinoid Type 1 Receptor-Induced Insulin Resistance and Gluconeogenesis

1
Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea
2
Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 50612, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(4), 968; https://doi.org/10.3390/ijms19040968
Received: 16 February 2018 / Revised: 16 March 2018 / Accepted: 21 March 2018 / Published: 23 March 2018
(This article belongs to the Special Issue Plant Natural Products for Human Health)
Activation of the hepatic cannabinoid type 1 receptor (CB1R) induces insulin resistance and gluconeogenesis via endoplasmic reticulum (ER) stress, thereby contributing to hyperglycemia. Gomisin N (GN) is a phytochemical derived from Schisandra chinensis. In the current study, we investigated the inhibitory effects of GN on hepatic CB1R-mediated insulin resistance and gluconeogenesis in 2-arachidonoylglycerol (AG; an agonist of CB1R)-treated HepG2 cells and in high-fat diet (HFD)-induced obese mice. Treatment with 2-AG induced the expression of ER stress markers, serine/threonine phosphatase PHLPP1, Lipin1, and ceramide synthesis genes, but reduced the expression of ceramide degradation genes in HepG2 cells. However, GN reversed 2-AG-mediated effects and improved the 2-AG-mediated impairment of insulin signaling. Furthermore, GN inhibited 2-AG-induced intracellular triglyceride accumulation and glucose production in HepG2 cells by downregulation of lipogenesis and gluconeogenesis genes, respectively. In vivo, GN administration to HFD obese mice reduced the HFD-induced increase in fasting blood glucose and insulin levels, which was accompanied with downregulation of HFD-induced expression of CB1R, ER stress markers, ceramide synthesis gene, and gluconeogenesis genes in the livers of HFD obese mice. These findings demonstrate that GN protects against hepatic CB1-mediated impairment of insulin signaling and gluconeogenesis, thereby contributing to the amelioration of hyperglycemia. View Full-Text
Keywords: cannabinoid type 1 receptor; endoplasmic reticulum stress; gluconeogenesis; gomisin N; lipogenesis; insulin resistance cannabinoid type 1 receptor; endoplasmic reticulum stress; gluconeogenesis; gomisin N; lipogenesis; insulin resistance
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MDPI and ACS Style

Nagappan, A.; Jung, D.Y.; Kim, J.-H.; Jung, M.H. Protective Effects of Gomisin N against Hepatic Cannabinoid Type 1 Receptor-Induced Insulin Resistance and Gluconeogenesis. Int. J. Mol. Sci. 2018, 19, 968. https://doi.org/10.3390/ijms19040968

AMA Style

Nagappan A, Jung DY, Kim J-H, Jung MH. Protective Effects of Gomisin N against Hepatic Cannabinoid Type 1 Receptor-Induced Insulin Resistance and Gluconeogenesis. International Journal of Molecular Sciences. 2018; 19(4):968. https://doi.org/10.3390/ijms19040968

Chicago/Turabian Style

Nagappan, Arulkumar; Jung, Dae Y.; Kim, Ji-Hyun; Jung, Myeong H. 2018. "Protective Effects of Gomisin N against Hepatic Cannabinoid Type 1 Receptor-Induced Insulin Resistance and Gluconeogenesis" Int. J. Mol. Sci. 19, no. 4: 968. https://doi.org/10.3390/ijms19040968

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