The caffeoylquinic acid-rich Pandanus tectorius fruit extract increases insulin sensitivity and regulates hepatic glucose and lipid metabolism in diabetic db/db mice

Abstract

Caffeoylquinic acids (CQAs) are widely distributed in various foods. While some CQAs have been shown to possess antihyperglycemic activities, whether it is beneficial for diabetes patients to ingest CQA-rich foods has still to be known. In this work, the antihyperglycemic and antihyperlipidemic effects of CQA-rich Pandanus tectorius fruit extract (PTF) was investigated in diabetic db/db mice. Treatment with PTF (200 mg/kg) significantly decreased body weight and fasting glucose level, alleviated hyperinsulinism and hyperlipidemia and declined glucose area under the curve in oral glucose tolerance test and insulin tolerance test. The elevated levels of serum proinflammatory cytokines and islet hypertrophy in db/db mice were remarkably attenuated by PTF treatment. Biochemical analysis showed that administration of PTF significantly stimulated the phosphorylation of AMP-activated protein kinase (AMPK) and Akt substract of 160 kDa (AS160), and enhanced the expression and translocation of glucose transporter type 4 (GLUT4) in skeletal muscles. It also increased the activity of hexokinase, decreased the expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase and switched the transcription of several key lipid metabolic genes in the liver, which, in turn, improved hepatic glucose and lipid profiles as determined by nuclear magnetic resonance-based metabolomics. Overall, the CQA-rich PTF is beneficial for the treatment of diabetes. It may alleviate hyperglycemia and dyslipidemia via activation of AMPK-AS160-GLUT4 pathway in skeletal muscles and inhibition of gluconeogenesis and lipogenesis in the liver.

Keywords: AMPK; Caffeoylquinic acid; Diabetes; GLUT4; Hyperlipidemia; Pandanus tectorius fruit.