Diet supplementation with green tea extract epigallocatechin gallate prevents progression to glucose intolerance in db/db mice

Abstract

BackgroundGreen tea was suggested as a therapeutic agent for the treatment of diabetes more than 70 years ago, but the mechanisms behind its antidiabetic effect remains elusive. In this work, we address this issue by feeding a green tea extract (TEAVIGO™) with a high content of epigallocatechin gallate (EGCG) or the thiazolidinedione PPAR-γ agonist rosiglitazone, as positive control, to db/db mice, an animal model for diabetes.MethodsYoung (7 week-old) db/db mice were randomized and assigned to receive diets supplemented with or without EGCG or rosiglitazone for 10 weeks. Fasting blood glucose, body weight and food intake was measured along the treatment. Glucose and insulin levels were determined during an oral glucose tolerance test after 10 weeks of treatment. Pancreata were sampled at the end of the study for blinded histomorphometric analysis. Islets were isolated and their mRNA expression analyzed by quantitative RT-PCR.ResultsThe results show that, in db/db mice, EGCG improves glucose tolerance and increases glucose-stimulated insulin secretion. EGCG supplementation reduces the number of pathologically changed islets of Langerhans, increases the number and the size of islets, and heightens pancreatic endocrine area. These effects occurred in parallel with a reduction in islet endoplasmic reticulum stress markers, possibly linked to the antioxidative capacity of EGCG.ConclusionsThis study shows that the green tea extract EGCG markedly preserves islet structure and enhances glucose tolerance in genetically diabetic mice. Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes.

Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications

“…Antidiabetic or lipid lowering properties of green tea or EGCG have been demonstrated in rodent models of type 2 diabetes as well as obesity (26,76,84,94). In diabetic db/db mice, EGCG increases the size and number of pancreatic islets and improves ␤-cell morphology, leading to better glucose tolerance comparable to rosiglitazone (63). Moreover, in human subjects who smoke or those with coronary artery disease, consumption of green tea significantly reverses their endothelial dysfunction (59,88).…”

Glutamate pathways of the beta-cell and the control of insulin secretion

“…In human pancreatic islets stimulated with high glucose, EGCG lowers insulin secretion along with a decrease of intracellular glutamate [23]. EGCG has been shown to reduce the body weight of obese subjects [24] and of various animal models [25,26], as well as to improve glucose tolerance in diabetic db/db mice [27]. However, the poor bioavailability of EGCG may limit its use and human trials have shown some inconsistencies [26,28].…”

Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System

“…Curcumin improved insulin resistance and glucose tolerance in type 2 diabetic db/db mice but not in nondiabetic db/+ mice (Seo et al, 2008). Green tea extract containing EGCG markedly improved glucose tolerance and increased glucose-stimulated insulin secretion by preserving islet structure in diabetic db/db (leptin receptor mutant) mice (Wolfram et al, 2006;Ortsäter et al, 2012). The natural flavonoids quercitrin, quercetin, and genistein attenuated hyperglycemia and increased insulin sensitivity in a mouse model of diabetes (Lee, 2006;Kobori et al, 2009;Babujanarthanam et al, 2010).…”