Green Tea Polyphenols Modulate Insulin Secretion by Inhibiting Glutamate Dehydrogenase

The Children's Hospital of Philadelphia, Filadelfia, Pennsylvania, United States
Journal of Biological Chemistry (Impact Factor: 4.57). 05/2006; 281(15):10214-21. DOI: 10.1074/jbc.M512792200
Source: PubMed


Insulin secretion by pancreatic β-cells is stimulated by glucose, amino acids, and other metabolic fuels. Glutamate dehydrogenase
(GDH) has been shown to play a regulatory role in this process. The importance of GDH was underscored by features of hyperinsulinemia/hyperammonemia
syndrome, where a dominant mutation causes the loss of inhibition by GTP and ATP. Here we report the effects of green tea
polyphenols on GDH and insulin secretion. Of the four compounds tested, epigallocatechin gallate (EGCG) and epicatechin gallate
were found to inhibit GDH with nanomolar ED50 values and were therefore found to be as potent as the physiologically important inhibitor GTP. Furthermore, we have demonstrated
that EGCG inhibits BCH-stimulated insulin secretion, a process that is mediated by GDH, under conditions where GDH is no longer
inhibited by high energy metabolites. EGCG does not affect glucose-stimulated insulin secretion under high energy conditions
where GDH is probably fully inhibited. We have further shown that these compounds act in an allosteric manner independent
of their antioxidant activity and that the β-cell stimulatory effects are directly correlated with glutamine oxidation. These
results demonstrate that EGCG, much like the activator of GDH (BCH), can facilitate dissecting the complex regulation of insulin
secretion by pharmacologically modulating the effects of GDH.

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