Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β -Cell Mass in Middle-Aged Obese Diabetic Mice.

Hana Alkhalidy,Yanling Zhang,Matthew Hulver,Dongmin Liu,Kyung-Shin Suh,Aihua Wang,William Moore,Zhiyong Cheng,Mostafa Ali,Zhenquan Jia,Ryan Mcmillan,Wei Zhen

doi:10.1155/2015/532984

Hana Alkhalidy, Yanling Zhang + Show 10 more

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https://doi.org/10.1155/2015/532984

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Abstract

Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice. In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreatic β-cell dysfunction.

Highlights

RDiabetes mellitus is a growing public health concern, prescausing increased intracellular fat content in skeletal muscle, liver, fat, and pancreatic islets
Using another mouse model of type 2 diabetes (T2D) generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass
T We recently demonstrated that kaempferol treatment prevented apoptosis and improved insulin biosynthesis and secretion in β-cells and human islets exposed to chronic hyperlipidemia [12]

Summary

Introduction

RDiabetes mellitus is a growing public health concern, prescausing increased intracellular fat content in skeletal muscle, liver, fat, and pancreatic islets. While the availability of novel drugs, techniques, and surgical and significant loss of functional β-cells [4,5,6,7,8]. Those intervention has improved the survival rate of individuals individuals with T2D always manifest increased β-cell apopwith diabetes, the prevalence of diabetes is still rising in tosis and reduced β-cell mass [6, 7, 9]. Prevent the onset of diabetes [10] Both in experimental animals and people, obesity is a leading T2D is a result of chronic and β-cell survival may provide a more effective strategy to insulin resistance and loss of β-cell mass and function [4]. prevent the onset of diabetes [10].

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