Since immunoassays cannot specifically quantify
Since immunoassays cannot specifically quantify each apelin peptide, a more reliable approach, mass spectrometry (MS) has been used recently to quantify and characterize apelin fragments in plasma. Using this technology, Zhen et al. showed that [Pyr-1]-apelin-13 was the major apelin form present in plasma of healthy subjects at concentrations ranging from 7.7 to 23.3pg/ml (Zhen et al., 2013). However, it is noteworthy that a previous study using HPLC-MS did not detect any apelin fragments in the plasma of healthy persons (Mesmin et al., 2010) whereas this approach successfully identified 46 different apelin peptides in bovine colostrum (Mesmin et al., 2011).
Plasma apelin concentrations in diabetes Numerous studies have reported plasma apelin concentrations in obese and/or diabetic subjects (for review see (Castan-Laurell et al., 2011)) and their number is still increasing. Most of the studies have shown higher apelin concentrations in type 2 diabetic patients compared to controls. Only two studies found low concentrations in newly diagnosed type 2 diabetic patients (Erdem et al., 2008, Zhang et al., 2009). Very recently it has been shown that there was a negative correlation between apelin levels and glycosylated hemoglobin in type 2 diabetic patients (Habchi et al., 2014). These results underline the role played by apelin in glycaemic balance and insulin sensitivity. Few studies have however reported the concentrations in type 1 diabetic patients and did the comparison with type 2 diabetic patients. In a first report, Alexiadou et al. (2012) showed that fasting plasma apelin concentrations were higher in type 1 diabetic patients compared to healthy subjects. However, apelin levels in diabetic subjects were not modified during an oral amantadine hcl tolerance test suggesting that they were not affected by high blood glucose. Recently plasma apelin concentrations were measured in both type 1 and type 2 diabetic subjects. Habchi et al. also showed that apelin concentrations were significantly higher in type 1 diabetic patients than in controls and even higher than in type 2 diabetic patients. Cavallo et al. reported different results: Type 2, but not type 1 diabetic patients, had increased serum apelin concentrations compared to non-diabetic subjects. (Cavallo et al., 2012). These discrepancies for type 1 diabetes could be explained by the differences in the population studied (age, body mass index and diabetes duration). The two studies showing increased concentrations of apelin in type 1 diabetes lead to interesting remarks. First, these results pointed out that obesity is probably not a main determinant of plasma apelin levels as previously reported (Castan-Laurell et al., 2011) and confirmed recently (Krist et al., 2013, Ma et al., 2014). Moreover, the higher concentrations of apelin found in type 1 diabetic subjects could be an attempt to compensate for the lack of insulin and to overcome insulin resistance. However patients were also treated with insulin that could as well explain this rise since insulin up regulates apelin gene expression. Further studies are needed to explore this relationship between apelin and type 1 diabetes. Interestingly, plasma apelin has been shown to be a novel biomarker for predicting diabetes (Ma et al., 2014). More than four hundred subjects (Han Chinese) were enrolled in this study performed at the National Taiwan University. Plasma apelin concentrations were higher in women than in men but they were associated with a risk of diabetes only in men. However, these data need to be confirmed and extended to other ethnic groups .
Acknowledgments This work was supported by Institut National de la Santé Et de la Recherche Médicale (INSERM). Original work realized in our team have received financial support from the SFD (Francophone Diabetes Society) and the SFN (French Nutrition Society).
Introduction It is becoming increasingly clear that adipocytes, previously thought as the mere energy storage sites, play pivotal roles in regulating energy metabolism through secretion of a variety of signaling molecules called adipokines (Fruhbeck et al., 2001, Lago et al., 2009). Secretion of adipokines is highly regulated and they are implicated with metabolic disorders, such as, obesity and diabetes mellitus (Matsuzawa, 2007, Ouchi et al., 2011, Than et al., 2011a). Apelin, which has been known to be secreted by several cell types (e.g., neurons (Reaux et al., 2001), cardiomyocytes (Chen et al., 2003), endothelial cells (Kleinz and Davenport, 2004), is identified as a new member of the adipokine family (Boucher et al., 2005, Wei et al., 2005).