Apelin Levels Are Increased in Morbidly Obese Subjects with Type 2 Diabetes Mellitus

Servicio de Endocrinología y Nutrición, Hospital Regional Universitario Carlos Haya, Málaga, Spain.
Obesity Surgery (Impact Factor: 3.75). 09/2009; 19(11):1574-80. DOI: 10.1007/s11695-009-9955-y
Source: PubMed


The physiological role of apelin in obesity and diabetes remains unclear. Although apelin has been studied in persons with different conditions, no studies have yet examined the joint influence of obesity and diabetes on apelin levels. We measured the changes in apelin levels in morbidly obese subjects, with and without diabetes, and in the inverse situation of improvement in carbohydrate metabolism as a result of bariatric surgery.
The study was undertaken in 54 morbidly obese persons, 16 of whom had type 2 diabetes mellitus, before and 7 months after undergoing bariatric surgery, and in 12 healthy, nonobese persons. Measurements were made of apelin levels and insulin sensitivity by an intravenous glucose tolerance test.
The apelin levels in the morbidly obese patients prior to surgery were significantly higher than those of the controls only when the morbidly obese subjects were diabetic (P < 0.005). Apelin levels correlated significantly in the morbidly obese patients with serum triglycerides (r = 0.292, P = 0.032) and glucose (r = 0.337, P = 0.039). Bariatric surgery resulted in a significant decrease in apelin levels only in the morbidly obese subjects with impaired fasting glucose or diabetes. The change in apelin levels correlated significantly in the morbidly obese patients with the changes in serum glucose (r = 0.338, P = 0.038) and insulin sensitivity (r = -0.417, P = 0.043).
This study demonstrates that obesity is not the main determinant of the rise in apelin levels. The association between apelin levels and glucose concentrations and insulin sensitivity provides evidence that apelin may play a role in the pathogenesis of diabetes.

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    • "In recent years, apelin has been linked to states of insulin resistance. In clinical studies, it has been reported that the levels of plasma apelin were elevated in insulin-resistant subjects [18] and in morbidly obese individuals with type 2 diabetes [19], [20], compared with normal controls. However, several recent studies have shown decreased plasma apelin concentrations in newly diagnosed and untreated patients with type 2 diabetes [21], [22]. "
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    ABSTRACT: Apelin, a novel adipokine, is the specific endogenous ligand of G protein-coupled receptor APJ. Consistent with its putative role as an adipokine, apelin has been linked to states of insulin resistance. However, the function of apelin in hepatic insulin resistance, a vital part of insulin resistance, and its underlying mechanisms still remains unclear. Here we define the impacts of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes. Our studies indicate that apelin reversed TNF-α-induced reduction of glycogen synthesis in HepG2 cells, mouse primary hepatocytes and liver tissues of C57BL/6J mice by improving JNK-IRS1-AKT-GSK pathway. Moreover, Western blot revealed that APJ, but not apelin, expressed in the hepatocytes and liver tissues of mice. We found that F13A, a competitive antagonist for G protein-coupled receptor APJ, suppressed the effects of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes, suggesting APJ is involved in the function of apelin. In conclusion, we show novel evidence suggesting that apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ. Apelin appears as a beneficial adipokine with anti-insulin resistance properties, and thus as a promising therapeutic target in metabolic disorders.
    PLoS ONE 08/2013; 8(2):e57231. DOI:10.1371/journal.pone.0057231 · 3.23 Impact Factor
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    • "In a study, diabetic morbidly obese patients had significantly higher plasma apelin levels than non-diabetic non-obese healthy subjects. After bariatric surgery, plasma apelin levels in morbidly obese subjects with impaired blood glucose were significantly decreased (Soriguer et al., 2009). Krist et al. (2013) also demonstrated that bariatric surgery dramatically decreased the apelin expression in adipose tissues and serum apelin levels, which significantly correlated with improved insulin sensitivity. "
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    ABSTRACT: Over a third of the US population is obese and at high risk for developing type 2 diabetes, insulin resistance, and other metabolic disorders. Obesity is considered a chronic low-grade inflammatory condition that is primarily attributed to expansion and inflammation of adipose tissues. Indeed, adipocytes produce and secrete numerous proinflammatory and anti-inflammatory cytokines known as adipokines. When the balance of these adipokines is shifted toward higher production of proinflammatory factors, local inflammation within adipose tissues and subsequently systemic inflammation occur. These adipokines including leptin, visfatin, resistin, apelin, vaspin, and retinol binding protein-4 can regulate inflammatory responses and contribute to the pathogenesis of diabetes. These effects are mediated by key inflammatory signaling molecules including activated serine kinases such as c-Jun N-terminal kinase and serine kinases inhibitor κB kinase and insulin signaling molecules including insulin receptor substrates, protein kinase B (PKB, also known as Akt), and nuclear factor kappa B. Bariatric surgery can decrease body weight and improve insulin resistance in morbidly obese subjects. However, despite reports suggesting reduced inflammation and weight-independent effects of bariatric surgery on glucose metabolism, mechanisms behind such improvements are not yet well understood. This review article focuses on some of these novel adipokines and discusses their changes after bariatric surgery and their relationship to insulin resistance, fat mass, inflammation, and glucose homeostasis.
    Frontiers in Endocrinology 06/2013; 4:69. DOI:10.3389/fendo.2013.00069
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    • "In line with these findings, an increase plasma apelin level was reported in morbidly obese subjects [17]. Moreover, apelin plasma level was found to be higher in obese diabetic patients compared to non-diabetic obese subjects [39]. Accordingly, growing evidence suggest that the APL/APJ system plays important roles in glucose metabolism and insulin sensitivity regulations. "
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    ABSTRACT: It has been proposed that the apelinergic system (apelin and its receptor APJ) may be a promising therapeutic target in obesity-associated insulin resistance syndrome. However, due to the extended tissue-distribution of this system, the therapeutic use of specific ligands for APJ may target numerous tissues resulting putatively to collateral deleterious effects. To unravel specific tissular dysfunctions of this system under obesity and insulin-resistance conditions, we measured the apelinemia and gene-expression level of both apelin (APL) and APJ in 12-selected tissues of insulin-resistant obese female mice fed with a high fat (HF) diet. In a preliminary study, we compared between adult male and female mice, the circadian plasma apelin variation and the effect of fasting on apelinemia. No significant differences were found for these parameters suggesting that the apelinemia is not affected by the sex. Moreover, plasma apelin level was not modulated during the four days of the estrous cycle in females. In obese and insulin-resistant HF female mice, plasma apelin concentration after fasting was not modified but, the gene-expression level of the APL/APJ system was augmented in the white adipose tissue (WAT) and reduced in the brown adipose tissue (BAT), the liver and in kidneys. BAT apelin content was reduced in HF female mice. Our data suggest that the apelinergic system may be implicated into specific dysfunctions of these tissues under obesity and diabetes and that, pharmacologic modulations of this system may be of interest particularly in the treatment of adipose, liver and renal dysfunctions that occur during these pathologies.
    Peptides 06/2013; 46. DOI:10.1016/j.peptides.2013.05.013 · 2.62 Impact Factor
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