Adenosine and adenosine-5\u2032-monophosphate ingestion ameliorates abnormal glucose metabolism in mice fed a high-fat diet

Ardiansyah Ardiansyah,Hitoshi Shirakawa,Afifah Zahra Agista,Michio Komai,Takuya Koseki,Tomoko Goto,Ikuo Ikeda,Yuto Inagawa

doi:10.1186/s12906-018-2367-6

Abstract

BackgroundWe have previously reported that ingestion of adenosine (ADN) and adenosine-5′-monophosphate (AMP) improves abnormal glucose metabolism in the stroke-prone spontaneously hypertensive rat model of non-obesity-associated insulin resistance. In this study, we investigated the effect of ADN and AMP ingestion on glucose metabolism in mice with high-fat diet-induced obesity.MethodsSeven-week-old C57BL/6 J mice were administered distilled water (as a control), 10 mg/L ADN, or 13 mg/L AMP via their drinking water for 14 or 25 weeks, during which they were fed a high-fat diet. Oral glucose tolerance test (OGTT) was conducted on 21-week-old mice fasted for 16 h. Insulin tolerance test (ITT) was performed on 22-week-old mice fasted for 3 h. Blood and muscle were collected for further analysis of serum parameters, gene and protein expression levels, respectively.ResultsGlucose metabolism in the ADN and AMP groups was significantly improved compared with the control. OGTT and ITT showed that ADN and AMP groups lower than control group. Furthermore, phosphorylation of AMP-activated protein kinase (AMPK) and mRNA levels of genes involved in lipid oxidation were enhanced in the skeletal muscle of ADN- and AMP-treated mice.ConclusionThese results indicate that ingestion of ADN or AMP induces activation of AMPK in skeletal muscle and mitigates insulin resistance in mice with high-fat diet-induced diabetes.

Highlights

We have previously reported that ingestion of adenosine (ADN) and adenosine-5′-monophosphate (AMP) improves abnormal glucose metabolism in the stroke-prone spontaneously hypertensive rat model of nonobesity-associated insulin resistance
We found that ingestion of ADN and AMP activates AMPactivated protein kinase (AMPK) in skeletal muscle and ameliorates insulin resistance and impaired glucose metabolism
The ratio of p-AMPK α-subunit (AMPKα) to total AMPKα (t-AMPKα) was significantly higher in the ADN and AMP groups than in the control group after 14 and 25 weeks of treatment (Fig. 5e). These results suggest that administration of ADN or AMP enhanced AMPK activity in skeletal muscle. mRNA levels of peroxisome proliferator-activated receptor α (Pparα) were significantly increased after

Summary

Introduction

We have previously reported that ingestion of adenosine (ADN) and adenosine-5′-monophosphate (AMP) improves abnormal glucose metabolism in the stroke-prone spontaneously hypertensive rat model of nonobesity-associated insulin resistance. We investigated the effect of ADN and AMP ingestion on glucose metabolism in mice with high-fat diet-induced obesity. The prevalence of obesity has increased because of changing lifestyles, including dietary habits, in both developed and developing countries [1]. Excessive energy intake causes increased presence of non-esterified fatty acids in the blood and diacylglycerol and palmitoyl-CoA in the liver and skeletal. Adenosine-5′-monophosphate (AMP)activated protein kinase (AMPK) has been reported to attenuate insulin resistance, since it enhances lipid oxidation and glucose uptake in the liver and skeletal muscle, in which it regulates the expression of β-oxidation-associated genes. Much attention is being paid to AMPK as a potential therapeutic target in the treatment of insulin resistance [6, 7].

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