Antidiabetic effect of gomisin N via activation of AMP-activated protein kinase

Jung, Dae Young; Kim, Jihyun; Lee, Hoyoung; Jung, Myeong Ho

doi:10.1016/j.bbrc.2017.10.120

Cited by 19 publications

(16 citation statements)

References 17 publications

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“…Thus, pharmacological inhibition of CB1R improves HFD-induced hyperglycemia and glucose tolerance. Previously, we demonstrated that GN reduced the HFD-induced hyperglycemia and improved the glucose tolerance in HFD obese mice [ 13 ]. In the current study, we examined whether GN-mediated improvement of hyperglycemia and glucose tolerance is through the inhibition of hepatic CB1R-mediated insulin resistance and gluconeogenesis.…”

Section: Resultsmentioning

confidence: 99%

“…GN is a phytochemical derived from S. chinensis , a traditional medicinal herb [ 11 ]. Previously, we demonstrated that GN exerts protective effects against HFD-induced hyperglycemia and hepatic steatosis in HFD obese mice [ 12 , 13 , 14 ]. In the present study, we investigated whether GN-mediated improvement of hyperglycemia and hepatic steatosis is through inhibition of the hepatic CB1R signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Gomisin N (GN), a lignan derived from S. chinensis , possesses hepatoprotective, anti-cancer, and anti-inflammatory effects [ 11 ]. Recently, we reported that GN exerts protective effects against obesity-induced hepatic steatosis and hyperglycemia through inhibition of ER stress and AMP-activated protein kinase (AMPK) activation, respectively [ 12 , 13 ]. As activation of hepatic CB1R signaling has been implicated in the development of insulin resistance, hyperglycemia, and hepatic steatosis, targeted inhibition of hepatic CB1R signaling might provide therapeutic approaches to restore insulin receptor signaling and improve hyperglycemia and hepatic steatosis.…”

Section: Introductionmentioning

confidence: 99%

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

Nagappan

Jung

Kim

et al. 2018

IJMS

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Nagappan

Jung

Kim

et al. 2018

IJMS

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“…Our results successfully demonstrate a beneficial effect of GN on reversing the devastating effect of a high-fat diet on the viability of affected animals. Recent reports indicate the pharmacological effect of GN on the prevention of hepatic steatosis in high-fat diet-fed mice [ 10 , 29 ]. Here, we provide another layer of experimental evidence to support the anti-obesity effect of GN by utilizing Drosophila , a well-established in vivo animal model to study molecular mechanisms underlying various human disorders.…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of Gomisin N in High-Fat-Induced Drosophila Obesity Models

Lee

Cheon

2020

IJMS

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Gomisin N (GN) is lignin derived from Schisandra chinensis that has been reported to exhibit hepato-protective, anti-cancer, and anti-inflammatory effects. However, its role in whole-body energetic homeostasis remains unclear. In this study, we employed Drosophila melanogaster as a diet-induced obese model to elucidate the effects of GN on lipid and glucose metabolism by measuring climbing activity, triglyceride levels, and lifespan under a rearing condition of a high-fat diet (HFD) containing 20% coconut oil, with or without GN. Constant exposure of flies to an HFD resulted in increased body weight and decreased climbing activity, along with a shortened life span. Importantly, the administration of GN to HFD groups lowered their body weight and induced a specific upregulation of lipid storage droplet (Lsd)-2 and hormone-sensitive lipase (Hsl), in addition to improved lifespan. Importantly, GN in HFD groups appeared to downregulate heat shock protein Hsp90 family member (dGRP94), a key regulator of the endoplasmic reticulum stress response, which may also contribute to improved life span in the presence of GN. Taken together, these in vivo findings suggest that GN could serve as a useful agent for the prevention and treatment of obesity.

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“…AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase and acts as a sensor of cellular energy status. Accumulating evidence reveals that AMPK regulates a wide variety of gene expression and metabolic signaling pathways [ 9 , 10 ]. Moreover, AMPK plays a pathophysiological role in lipoatrophic diabetes [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Reduced Beta 2 Glycoprotein I on Liver Injury in Streptozotocin (STZ)-Diabetic Rats by Activation of AMP-Activated Protein Kinase

Zhang

et al. 2018

Med Sci Monit

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BackgroundProtective effects of reduced beta 2 glycoprotein I (Rβ2GPI) against vascular injury of diabetes mellitus have been extensively investigated. However, the effects of Rβ2GPI on liver injury in diabetic animals have not been reported.Material/MethodsA diabetic rat model of was produced by systemic injection of streptozotocin (STZ). Rats were divided into a normal control group, a model group, and an Rβ2GPI treatment group (N=6 in each group). After treatments, blood serum and liver tissue were collected to test the protection of Rβ2GPI. AMP-activated protein kinase (AMPK) was detected by immunohistochemistry and Western blotting.ResultsOur results revealed that Rβ2GPI reduced blood glucose, serum creatinine, and urea nitrogen levels, as well as serum inflammation cytokines, including interleukin (IL)-6, tumor necrosis factor (TNF)-a and C-reactive protein in the diabetic rats. Importantly, Rβ2GPI prevented liver injury in the diabetic rats as confirmed by hematoxylin-eosin (H&E) staining, alanine transaminase, aspartate transaminase, and gamma-glutamyl transferase. Reactive oxygen species (ROS) were promoted by diabetic modeling and were attenuated by Rβ2GPI administration. Moreover, Rβ2GPI significantly reduced liver catalase, malondialdehyde, and superoxide dismutase levels in the diabetic rats. Rβ2GPI reduced liver glycolipid storage in STZ diabetic rats. Both immunohistochemistry and Western blotting demonstrated that Rβ2GPI promoted AMPK phosphorylation in the diabetic rats.ConclusionsOur data proved that Rβ2GPI prevented liver injury in diabetic rats, likely through activating the AMPK signaling pathway.

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Antidiabetic effect of gomisin N via activation of AMP-activated protein kinase

Cited by 19 publications

References 17 publications

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

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

Functional Characterization of Gomisin N in High-Fat-Induced Drosophila Obesity Models

Protective Effects of Reduced Beta 2 Glycoprotein I on Liver Injury in Streptozotocin (STZ)-Diabetic Rats by Activation of AMP-Activated Protein Kinase

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