Apelin levels are increased in morbidly obese subjects with type 2 diabetes mellitus.
ABSTRACT 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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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 · 2.61 Impact Factor
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ABSTRACT: Apelin, an adipocyte-secreted factor upregulated by insulin, is increased in adipose tissue (AT) and plasma with obesity. Apelin was recently identified as a new player in the control of glucose homeostasis. However, the regulation of apelin and APJ (apelin receptor) expression in skeletal muscle in relation to insulin resistance or type 2 diabetes is not known. Thus we studied apelin and APJ expression in AT and muscle in different mice models of obesity and in type 2 diabetic patients. In insulin-resistant high-fat (HF)-fed mice, apelin and APJ expression were increased in AT compared with control. This was not the case in AT of highly insulin-resistant db/db mice. In skeletal muscle, apelin expression was similar in control and HF-fed mice and decreased in db/db mice. APJ expression was decreased in both HF-fed and db/db mice. Control subjects and type 2 diabetic patients were subjected to a hyperinsulinemic-euglycemic clamp, and tissues biopsies were obtained before and at the end of the clamp. There was no significant difference in basal apelin and APJ expression in AT and muscle between control and diabetic patients. However, apelin plasma levels were significantly increased in diabetic patients. During the clamp, hyperinsulinemia increased apelin and APJ expression in AT of control but not in diabetic subjects. In muscle, only APJ mRNA levels were increased in control but also in diabetic patients. Taken together, these data show that apelin and APJ expression in mice and humans is regulated in a tissue-dependent manner and according to the severity of insulin resistance.AJP Endocrinology and Metabolism 03/2010; 298(6):E1161-9. DOI:10.1152/ajpendo.00598.2009 · 4.09 Impact Factor
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ABSTRACT: Apelin is the endogenous ligand of the membrane G protein coupled receptor named APJ. Several isoforms of apelin exist, such as apelin-36 and apelin-13. Apelin and APJ are expressed in the central nervous system, particularly in the hypothalamus and in many peripheral tissues, such as heart, lung, adipose tissue, endothelial cells and skeletal muscle. Apelin is involved in regulation of fluid homeostasis, cardiovascular function, food intake, cell proliferation and angiogenesis. Apelin has recently been described by our group as a factor produced and secreted by adipocytes. The expression and the secretion of apelin in adipocytes are mainly regulated by insulin in humans and rodents. With obesity and associated diseases, such as diabetes type 2, plasma concentration of apelin is increased. The relationship between apelin and metabolic disorders is a new area of investigation. Recent data have highlighted a role of apelin, not only in carbohydrate but also in lipid metabolism. Apelin has emerged as a beneficial adipokine in obesity and diabetes. It therefore represents a promising therapeutic target in the treatment of metabolic disorders.Cahiers de Nutrition et de Diététique 09/2010; 45(4). DOI:10.1016/j.cnd.2010.05.002