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

• Published in: Antioxidants 2016-12, Vol.5 (4), p.47
• Main Authors: Meng, Ran, Mahadevan, Jana, Oseid, Elizabeth, Vallerie, Sara, Robertson, R Paul
• Format: Article
• Language: English
• Subjects: insulin; phosphodiesterase; silymarin
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox5040047

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 Ca /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.