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


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


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1

Pacific Northwest Diabetes Research Institute, Seattle, WA 98122, USA

2

Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA 98105, USA

3

Department of Pharmacology, University of Washington, Seattle, WA 98105, USA





*

Author to whom correspondence should be addressed.



Academic Editor: Francesca Giampieri

Abstract 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





Autor: Ran Meng 1, Jana Mahadevan 1, Elizabeth Oseid 1, Sara Vallerie 1 and R. Paul Robertson 1,2,3,*

Fuente: http://mdpi.com/



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