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Antioxidants 2016, 5(4), 47;

Silymarin Activates c-AMP Phosphodiesterase and Stimulates Insulin Secretion in a Glucose-Dependent Manner in HIT-T15 Cells

Pacific Northwest Diabetes Research Institute, Seattle, WA 98122, USA
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA 98105, USA
Department of Pharmacology, University of Washington, Seattle, WA 98105, USA
Author to whom correspondence should be addressed.
Academic Editor: Francesca Giampieri
Received: 4 October 2016 / Revised: 21 November 2016 / Accepted: 6 December 2016 / Published: 12 December 2016
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Silymarin (SIL) is a flavonoid extracted from milk thistle seed that has been reported to decrease hyperglycemia in people with type 2 diabetes (T2D). However, it is not known whether SIL has direct secretory effects on β-cells. Using the β-cell line HIT-T15, SIL was shown to decrease intracellular peroxide levels and to augment glucose-stimulated insulin secretion (GSIS). However, the latter was observed using a concentration range of 25–100 µM, which was too low to affect endogenous peroxide levels. The stimulatory effect of SIL dissipated at higher concentrations (100–200 µM), and mild apoptosis was observed. The smaller concentrations of SIL also decreased cAMP phosphodiesterase activity in a Ca2+/calmodulin-dependent manner. The stimulatory effects of SIL on GSIS were inhibited by three different inhibitors of exocytosis, indicating that SIL’s mechanism of stimulating GSIS operated via closing β-cell K-ATP channels, and perhaps more distal sites of action involving calcium influx and G-proteins. We concluded that augmentation of GSIS by SIL can be observed at concentrations that also inhibit cAMP phosphodiesterase without concomitant lowering of intracellular peroxides. View Full-Text
Keywords: insulin; phosphodiesterase; silymarin insulin; phosphodiesterase; silymarin

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Meng, R.; Mahadevan, J.; Oseid, E.; Vallerie, S.; Robertson, R.P. Silymarin Activates c-AMP Phosphodiesterase and Stimulates Insulin Secretion in a Glucose-Dependent Manner in HIT-T15 Cells. Antioxidants 2016, 5, 47.

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