Abstract
Previous studies have reported that levels of serum arginase I are increased in certain diseases. However, the exact association between arginase I and diabetes mellitus (DM) has yet to be determined. The aim of the present study was to investigate the correlation between arginase I activity and DM to determine whether arginase I activity may be used as a diagnostic biomarker for DM. DM was induced by a streptozotocin injection, while the arginase inhibitor, citrulline, was administered daily. Serum levels of glucose, reactive oxygen species (ROS) and arginase I activity were analyzed, and quantitative polymerase chain reaction and western blot analysis were performed to detect the mRNA and protein expression levels of arginase I, respectively. In addition, western blot analysis was used to determine the protein expression of the Tie 2 receptor. Pearson’s analysis was used to determine the correlation between arginase I activity and Tie 2 expression, while concordance analysis was performed using the Cohen’s test to obtain the Kappa statistic. The results demonstrated that serum arginase I activity levels in the rats with DM were significantly elevated compared with the control group, and positively correlated with the blood glucose levels. In addition, the blood glucose and ROS levels were increased significantly in the rats with DM. Arginase I mRNA and protein expression levels were significantly elevated in the diabetic rats when compared with the control group, and Tie 2 expression levels increased and were shown to correlate with arginase I activity in the diabetic rats. In addition, arginase I activity was shown to correlate with glucose intolerance and post-load glucose values. Good concordance was observed between arginase I activity and the clinical diagnosis for DM (κ=0.876; P<0.001). Therefore, the results indicated that arginase I may function as a diagnostic biomarker for DM rats model.
Highlights
Arginase enzymes play a major role in the biosynthesis of polyamines and amino acids, including ornithine, proline and glutamate [1,2]
Arginase I activity levels significantly correlated with the blood glucose levels in the diabetic rats (Fig. 1D; P
To the best of our knowledge, the present study is the first study investigating the potential role of arginase I as a diagnostic or prognostic marker for type 2 diabetes mellitus (DM)
Summary
Arginase enzymes play a major role in the biosynthesis of polyamines and amino acids, including ornithine, proline and glutamate [1,2]. Arginase has two distinct isoforms, arginase I and II, which differ in subcellular localization. Arginase I is predominantly localized in the cytosol of hepatic cells and is a key enzyme in the urea cycle. Arginase II is expressed in the mitochondria of extrahepatic cells and is encoded by a different gene [3]. The two arginases are constitutively expressed in cells and tissues, and indirectly regulate nitric oxide (NO) generation from nitric oxide synthase (NOS) by competition for a common enzyme substrate [4,5]. The induction of NOS arginase has been investigated in the inflammatory cells of asthmatic lungs as pathophysiological evidence that the consumption of L‐arginine by arginase may lead to the depletion of NO production and endothelial dysfunction; the enlargement of bronchial smooth muscle associated with airway hyperresponsiveness [6,7,8]. Following catabolism by arginase, arginine is no longer available to NOS; subsequent NO synthesis is diminished [9]
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