Structure-Dependent Inhibitory Effects of Green Tea Catechins on Insulin Secretion from Pancreatic β-Cells

Abstract

The effects of green tea catechins on glucose-stimulated insulin secretion (GSIS) were investigated in the β-cell line INS-1D. Epigallocatechin gallate (EGCG) at 10 µM or gallocatechin gallate (GCG) at 30 µM caused significant inhibitory effects on GSIS, and each of these at 100 µM almost abolished it. In contrast, epicatechin (EC) or catechin (CA) had no effect on GSIS at concentrations up to 100 µM. We thus investigated the structure-activity relationship by using epigallocatechin (EGC) and gallocatechin (GC) containing a trihydroxyl group in the B-ring, and epicatechin gallate (ECG) and catechin gallate (CG) containing the gallate moiety. EGC, GC, and ECG caused an inhibition of GSIS, although significant effects were obtained only at 100 µM. At this concentration, EGC almost abolished GSIS, whereas GC and ECG partially inhibited it. In contrast, CG did not affect GSIS at concentrations up to 100 µM. EGCG also abolished the insulin secretion induced by tolbutamide, an ATP-sensitive K channel blocker, and partially inhibited that induced by 30 mM K . Moreover, EGCG, but not EC, inhibited the oscillation of intracellular Ca 2 concentration induced by 11.1 mM glucose. These results suggest that some catechins at supraphysiological concentrations have inhibitory effects on GSIS, the potency of which depends on their structure; the order of potency was EGCG>GCG>EGC>GC≈ECG. The inhibitory effects seem to be mediated by the inhibition of voltagedependent Ca 2 channels, which is caused, at least in part, by membrane hyperpolarization resulting from the activation of K channels.

Evaluation of Viburnum opulus L. Fruit Phenolics Cytoprotective Potential on Insulinoma MIN6 Cells Relevant for Diabetes Mellitus and Obesity

“…Interestingly, at a low-glucose concentration (2 mM) both extracts were able to increase insulin secretion by 15-20%, but the FJ extract was still the stronger activator of that process. There is evidence showing that green tea catechins reveal an inhibitory influence on insulin secretion depending on their structure and concentration, but still are able to decrease hyperglycemia by elevating glucose uptake by cells [43]. The authors have suggested that the inhibitory effect of catechins on GSIS is caused by inhibition of voltage-dependent Ca 2+ channels, which is mediated partially by membrane hyperpolarization induced by the opening of K + channels.…”

Decrement in Cellular Iron and Reactive Oxygen Species, and Improvement of Insulin Secretion in a Pancreatic Cell Line Using Green Tea Extract

“…In comparison, the inhibitory effect of insulin secretion in an INS-1D β-cell line by EGCG was reported. 50 High doses of free radical scavengers and iron chelators were ineffective in relieving oxidative stress and were even found to be toxic to rat pancreatic cells. 51 Moreover, RIM5mF cells with a weak antioxidant defense and enhanced autophagocytosis were very sensitive to oxidants (eg, alloxan) while DFO prevented such toxic effects.…”

Influence of flavonoids on mechanism of modulation of insulin secretion

“…Catechin is a phytonutrient member of flavan family such as epicatechin (EC), epigallocatechin (EGC), epicatechin-3-gallate, and epigallocatechin-3-gallate. [ 84 ] Studies indicate that flavan-3-ol can exert both inhibitory activities[ 85 86 ] as stimulus for insulin secretion. [ 87 ] EC is found in large amounts in grape pomace[ 88 ] and has been considered a strong antioxidant.…”