Dr. Shirin Pournourmohammadi

Hjelt grant holder 2011, University of Geneva

Evaluating the green tea flavonoid epigallocatechin-3-gallate (EGCG) as a model substance for the treatment of type 2 diabetes

Dr. Shirin Pournourmohammadi, PhD, received a senior postdoctoral fellowship from the Foundation February 2011 to February 2013. Dr. Pournourmohammadi obtained her PhD in pharmacology/ toxicology in Tehran University, Iran, spending the last year of her thesis work in Professor P. Maechler’s group, University of Geneva. Thereafter, she was first assistant professor in pharmacology, Kerman University, Iran; subsequently associate professor, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia. The funded project conducted in Prof. Maechler’s group, aimed at evaluating the green tea flavonoid epigallocatechin-3-gallate (EGCG) as a model substance for the treatment of type 2 diabetes. Dr. Pournourmohammadi could demonstrate that EGCG inhibited glucose-stimulated insulin secretion by blocking the mitochondrial enzyme glutamate dehydrogenase. This enzyme generates the metabolic coupling factor glutamate and its genetic ablation inhibits glucose-stimulated insulin secretion. EGCG was without effect in the ablated mouse islets, proving that the compound acts by blocking glutamate dehydrogenase. The studies established a link between inhibition of glutamate dehydrogenase and stimulation of the energy-sensing enzyme adenosine monophosphate kinase (AMPK). Indeed, EGCG activated AMPK both in insulin producing beta cells and in muscle cells, where it exerted an insulin-like enhancement of glucose uptake. It is proposed that EGCG like-compounds could be used in the treatment of type 2 diabetes in patients with overweight, displaying increased insulin secretion and decreased insulin action in muscle and other insulin target tissues.

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