Alpha-Mangostin Improves Insulin Secretion and Protects INS-1 Cells from Streptozotocin-Induced Damage
AbstractAlpha (α)-mangostin, a yellow crystalline powder with a xanthone core structure, is isolated from mangosteen (Garcinia mangostana), which is a tropical fruit of great nutritional value. The aim of the present study was to investigate the anti-diabetic effects of α-mangostin and to elucidate the molecular mechanisms underlying its effect on pancreatic beta (β)-cell dysfunction. To assess the effects of α-mangostin on insulin production, rat pancreatic INS-1 cells were treated with non-toxic doses of α-mangostin (1–10 μM) and its impact on insulin signaling was examined by Western blotting. In addition, the protective effect of α-mangostin against pancreatic β-cell apoptosis was verified by using the β-cell toxin streptozotocin (STZ). Our results showed that α-mangostin stimulated insulin secretion in INS-1 cells by activating insulin receptor (IR) and pancreatic and duodenal homeobox 1 (Pdx1) followed by phosphorylation of phospho-phosphatidylinositol-3 kinase (PI3K), Akt, and extracellular signal regulated kinase (ERK) signaling cascades, whereas it inhibited the phosphorylation of insulin receptor substrate (IRS-1) (Ser1101). Moreover, α-mangostin was found to restore the STZ-induced decrease in INS-1 cell viability in a dose-dependent manner. In addition, treatment of INS-1 cells with 50 μM STZ resulted in an increase in intracellular reactive oxygen species (ROS) levels, which was represented by the fluorescence intensity of 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). This oxidative stress was decreased by co-treatment with 5 μM α-mangostin. Similarly, marked increases in the phosphorylation of P38, c-Jun N-terminal kinase (JNK), and cleavage of caspase-3 by STZ were decreased significantly by co-treatment with 5 μM α-mangostin. These results suggest that α-mangostin is capable of improving insulin secretion in pancreatic β-cells and protecting cells from apoptotic damage. View Full-Text
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Lee, D.; Kim, Y.-M.; Jung, K.; Chin, Y.-W.; Kang, K.S. Alpha-Mangostin Improves Insulin Secretion and Protects INS-1 Cells from Streptozotocin-Induced Damage. Int. J. Mol. Sci. 2018, 19, 1484.
Lee D, Kim Y-M, Jung K, Chin Y-W, Kang KS. Alpha-Mangostin Improves Insulin Secretion and Protects INS-1 Cells from Streptozotocin-Induced Damage. International Journal of Molecular Sciences. 2018; 19(5):1484.Chicago/Turabian Style
Lee, Dahae; Kim, Young-Mi; Jung, Kiwon; Chin, Young-Won; Kang, Ki S. 2018. "Alpha-Mangostin Improves Insulin Secretion and Protects INS-1 Cells from Streptozotocin-Induced Damage." Int. J. Mol. Sci. 19, no. 5: 1484.
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