The effect of green tea extract compounds on regulation of glucose homoeostasis in insulin-sensitive and breast cancer cells

Abstract

Green tea and its active constituents possess numerous health promoting properties, including regulation of glucose homoeostasis and anti-cancerous effects. However, the molecular mechanisms underpinning these properties are poorly understood. This study investigated the effects of green tea extracts on glucose metabolism in insulin-sensitive and breast cancer cells, and C57/BL mice. Glucose uptake in the presence and absence of protein kinase B (Akt) and adenosine 5’-monophosphate-activated protein kinase (AMPK) inhibitors, hepatic glycogenesis, triglyceride content, the rate of lipolysis, metabolic gene expression, and Akt and AMPK phosphorylations were assessed in mouse skeletal myotubes, adipocytes and hepatocytes. Epigallocatechin gallate (EGCG), epicatechin (EC), epicatechin gallate (ECG), quercetin, and combinations of these compounds selectively increased glucose uptake in these cell lines, and specific dose and time points of ECG and quercetin stimulated AML12 glycogenesis. EGCG, EC, and ECG suppressed adipocyte adipogenesis and lipolysis. These effects were mediated via AMPK in myotubes and Akt in adipocytes/hepatocytes cells. In mice fed a normal or glucose rich diet alongside decaffeinated green tea extract (DGTE), EGCG, and commercial green tea extract (GTE), markers related to glucose and lipid metabolism, body and tissues mass, and ingestion behaviour were assessed. DGTE and EGCG significantly reduced fasting glucose by 45.5% and 33.9% in a glucose fed mice. EGCG increased insulin level and accordingly increased measured of insulin resistance and beta cell function in normal fed mice, whilst, EGCG and GTE significantly increased insulin levels only in glucose-fed mice. Interestingly, selected extracts of green tea raised all adipose tissue masses. The significant increase in triglyceride contents were seen in mice fed a normal diet with DGTE and EGCG, and only EGCG with glucose diet. In breast cancer cells, cell viability, apoptosis, 2-NBDG uptake, lactate production, cellular migration, and phosphorylation of Akt and AMPK markers were explored. EGCG, experiment catechins, and quercetin significantly decreased cell viability, and induced apoptosis, whilst EGCG and quercetin showed reduced cell migration. EGCG and quercetin significantly decreased MCF7 and MDA-MB-231 glucose uptake associated with marked decrease in lactate production. To conclude, selected green tea compounds have significant potential anti-glycaemic, anti-diabetic, and anti-tumour properties, and exert their effects at least in part through Akt and AMPK signalling pathways.