Myricitrin Ameliorates Hyperglycemia, Glucose Intolerance, Hepatic Steatosis, and Inflammation in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.

Do Yeon Kim,Sang Ryong Kim,Un Ju Jung

doi:10.3390/ijms21051870

Abstract

To test the hypothesis that myricitrin (MYR) improves type 2 diabetes, we examined the effect of MYR on hyperglycemia, glucose intolerance, hepatic steatosis, and inflammation in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice. Male C57BL/6J mice were randomly divided into three groups: non-diabetic, diabetic control, and MYR (0.005%, w/w)-supplemented diabetic groups. Diabetes was induced by HFD and STZ, and MYR was administered orally for 5 weeks. Myricitrin exerted no significant effects on food intake, body weight, fat weight, or plasma lipids levels. However, MYR significantly decreased fasting blood glucose levels, improved glucose intolerance, and increased pancreatic β-cell mass compared to the diabetic control group. Myricitrin administration also markedly increased glucokinase mRNA expression and activity as well as lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase mRNA expression and activity in the liver. In addition, liver weight, hepatic triglyceride content, and lipid droplet accumulation were markedly decreased following MYR administration. These changes were seemingly attributable to the suppression of the hepatic lipogenic enzymes—fatty acid synthase and phosphatidate phosphohydrolase. Myricitrin also significantly lowered plasma MCP-1 and TNF-α levels and the mRNA expression of hepatic pro-inflammatory genes. These results suggest that MYR has anti-diabetic potential.

Highlights

Type 2 diabetes is characterized by impaired insulin secretion and activity [1], leading to multiple metabolic abnormalities including hyperglycemia in fasted and postprandial states
Insulin resistance affects hepatic lipid metabolism through several mechanisms, including the promotion of de novo lipogenesis in the liver, and insulin resistance is strongly associated with the development of non-alcoholic fatty liver disease (NAFLD) [3]
The DM group had significantly lower body weight gain, fat weight, and food efficiency ratio (FER) than the non-DM group, food intake did not differ between the two groups (Figure 1B–E)

Summary

Introduction

Type 2 diabetes is characterized by impaired insulin secretion and activity [1], leading to multiple metabolic abnormalities including hyperglycemia in fasted and postprandial states. The liver is an insulin-sensitive tissue that plays a central role in the maintenance of glucose homeostasis by regulating the interaction between glucose utilization and gluconeogenesis [2]. Dysregulation of hepatic glucose metabolism plays a crucial role in the pathogenesis and complications of diabetes [1]. Insulin resistance affects hepatic lipid metabolism through several mechanisms, including the promotion of de novo lipogenesis in the liver, and insulin resistance is strongly associated with the development of non-alcoholic fatty liver disease (NAFLD) [3]. Abnormal hepatic glucose and lipid metabolism are attractive therapeutic targets for type 2 diabetes

Methods

Results

Conclusion