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Beneficial metabolic effects of dietary epigallocatechin gallate alone and in combination with exendin-4 in high fat diabetic mice.

Abstract：

OBJECTIVE:Significant attempts are being made to generate multifunctional, hybrid or peptide combinations as novel therapeutic strategies for type 2 diabetes, however this presents key challenges including design and pharmaceutical development. In this study, we evaluated metabolic properties of oral nutritional supplement epigallocatechin gallate (EGCG) in combination with GLP-1 agonist exendin-4 in a mouse model of dietary-induced diabetes and obesity. METHODS:EGCG, exendin-4 or combination of both were administered twice-daily over 28 days to high fat (HF) mice on background of low-dose streptozotocin. Energy intake, body weight, fat mass, glucose tolerance, insulin sensitivity, lipid profile, biochemical and hormone markers, and islet histology were examined. RESULTS:All treatment groups exhibited significantly reduced body weight, fat mass, circulating glucose and insulin concentrations, and HbA1c levels which were independent of changes in energy intake. Similarly, there was marked improvement in glycaemic control, glucose-stimulated insulin release, insulin sensitivity, total cholesterol and triglycerides, with most prominent effects observed following combination therapy. Circulating corticosterone concentrations and 11beta-hydroxysteroid dehydrogenase type1 (11β-HSD1) staining (in pancreas) were beneficially decreased without changes in circulating interleukin 6 (IL-6), alanine transaminase (ALT) and glutathione reductase. Combination therapy resulted in increased islet area and number, beta cell area, and pancreatic insulin content. Generally, metabolic effects were much more pronounced in mice which received combination therapy. CONCLUSIONS:EGCG alone and particularly in combination with exendin-4 exerts positive metabolic properties in HF mice. EGCG may be useful dietary adjunct alongside GLP-1 mimetics in treatment of diabetes and related disorders.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Pathak NM,Millar PJB,Pathak V,Flatt PR,Gault VA

doi

10.1016/j.mce.2017.07.024

subject

Has Abstract

pub_date

2018-01-15 00:00:00

pages

200-208

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(17)30397-0

journal_volume

460

pub_type

杂志文章

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Beneficial metabolic effects of dietary epigallocatechin gallate alone and in combination with exendin-4 in high fat diabetic mice.