Abstract

This study investigated the effects of combined grape pomace and omija fruit extracts (GO) on diabetes-related metabolic changes in type 2 diabetic db/db mice. The effects of GO were compared with those of a resveratrol and schizandrin mixture (RS), which is a mixture of major components of GO. Mice were fed a normal diet with RS (0.005% resveratrol and 0.02% schizandrin in diet, w/w) or GO (0.3% grape pomace ethanol extract and 0.05% omija fruit ethanol extract in diet, w/w) for seven weeks. RS and GO not only lowered the levels of blood and plasma glucose, HbA1c, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) with a simultaneous decrease in hepatic gluconeogenic enzymes activities and adiposity, but also improved preservation of the pancreatic β-cells. Plasma leptin and resistin levels were lower while the plasma adiponectin level was higher in the RS and GO groups than in the control group. Especially, GO increased hepatic glucokinase activity and gene expression and improved hepatic steatosis by elevating fatty acid oxidation compared to RS. These findings suggest that GO ameliorates hyperglycemia, adiposity and hepatic steatosis in type 2 diabetic mice.

Highlights

  • Type 2 diabetes is one of the most common metabolic disorders

  • Hepatic insulin resistance is associated with hepatic steatosis, which is highly prevalent in patients with type 2 diabetes [2,3]

  • We found that GO significantly lowered the levels of blood and plasma glucose and HbA1c and decreased the homeostasis model assessment of insulin resistance (HOMA-IR) value, to or better than resveratrol and schizandrin mixture (RS) supplementation (Figure 1A–C)

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Summary

Introduction

Type 2 diabetes is one of the most common metabolic disorders. The pathogenesis of type 2 diabetes is characterized by a combination of impaired insulin secretion from pancreatic β-cells and insulin resistance. Grapes contain numerous polyphenols, including resveratrol, quercetin, catechins and anthocyanins, which have been shown to reduce blood glucose and improve pancreatic β-cell function [4]. We have investigated here if GO would lower body fat mass, and improve diabetes-related metabolic changes, including plasma biomarkers, β-cell failure and hepatic glucose-regulating enzymes in db/db mice. These mice display many of the characteristics of type 2 diabetes, including hyperphagia, hyperglycemia, β-cell loss and insulin resistance. Schizandrin is the main active ingredient of omija and has been shown to lower blood glucose level and improve insulin resistance in 90% pancreatectomized diabetic rats fed an HFD [10]

Results and Discussion
Preparation of Extracts
HPLC Analysis of Index Compounds
Animal and Diets
Plasma and Blood Biomarkers
Hepatic Enzymes Activities
RNA Extraction and Real-Time Quantitative PCR Analysis
Histopathological Analysis
Statistical Analysis
Conclusions

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