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: Apelin is an endogenous ligand of the human orphan receptor APJ. We detected apelin-like immunoreactivity in the adipocytes, gastric mucosa, and Kupffer cells in the liver. We also detected apelin-like immunoreactivity localized within the endothelia of small arteries in various organs. Further, it was found that mean arterial pressure after the administration of apelin-12, apelin-13, and apelin-36 at a dose of 10 nmol/kg in anaesthetized rats was reduced by 26±5, 11±4, and 5±4 mm Hg, respectively. In the presence of a nitric oxide (NO) synthase inhibitor, the effect of apelin-12 on blood pressure was abolished. Furthermore, the administration of apelin-12 (10 nmol/kg) in rats produced a transitory elevation of the plasma nitrite/nitrate concentration from a basal level of 21.4±1.6 to 27.0±1.5 μM. Thus, apelin may lower blood pressure via a nitric oxide-dependent mechanism.Regulatory Peptides 07/2001; · 2.06 Impact Factor
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ABSTRACT: Glucose tolerance depends on a complex interaction among insulin secretion from the beta-cells, clearance of the hormone, and the actions of insulin to accelerate glucose disappearance and inhibit endogenous glucose production. An additional factor, less well recognized, is the ability of glucose per se, independent of changes in insulin, to increase glucose uptake and suppress endogenous output (glucose effectiveness). These factors can be measured in the intact organism with physiologically based minimal models of glucose utilization and insulin kinetics. With the glucose minimal model, insulin sensitivity (SI) and glucose effectiveness (SG) are measured by computer analysis of the frequently sampled intravenous glucose tolerance test. The test involves intravenous injection of glucose followed by tolbutamide or insulin and frequent blood sampling. SI varied from a high of 7.6 x 10(-4) min-1.microU-1.ml-1 in young Whites to 2.3 x 10(-4) min-1.microU-1.ml-1 in obese nondiabetic subjects; in all of the nondiabetic subjects, SG was normal. In subjects with non-insulin-dependent diabetes mellitus (NIDDM), not only was SI reduced 90% below normal (0.61 +/- 0.16 x 10(-4) min-1.microU-1.ml-1), but in this group alone, SG was reduced (from 0.026 +/- 0.008 to 0.014 +/- 0.002 min-1); thus, defects in SI and SG are synergistic in causing glucose intolerance in NIDDM. One assumption of the minimal model is that the time delay in insulin action on glucose utilization in vivo is due to sluggish insulin transport across the capillary endothelium. This was tested by comparing insulin concentrations in plasma with those in lymph (representing interstitial fluid) during euglycemic-hyperinsulinemic glucose clamps. Lymph insulin was lower than plasma insulin at basal (12 vs. 18 microU/ml) and at steady state, indicating significant loss of insulin from the interstitial space, presumably due to cellular uptake of the insulin-receptor complex. Additionally, during clamps, lymph insulin changed more slowly than plasma insulin, but the rate of glucose utilization followed a time course identical with that of lymph (r = .96) rather than plasma (r = .71). Thus, lymph insulin, which may be reflective of interstitial fluid, is the signal to which insulin-sensitive tissues are responding. These studies support the concept that, at physiological insulin levels, the time for insulin to cross the capillary endothelium is the process that determines the rate of insulin action in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)Diabetes 01/1990; 38(12):1512-27. · 7.90 Impact Factor
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ABSTRACT: Hypercholesterolemia is a major risk factor for atherosclerosis. Dysregulation of adipokines contribute to atherosclerotic diseases. Apelin has recently been shown to be secreted by the adipose tissue in association with hyperinsulinemia and inflammation. We searched plasma apelin levels in patients with elevated low density lipoprotein (LDL)-cholesterol having no additional disorder. Thirty-three patients with hypercholesterolemia and 50 age-, sex-, and body mass index-matched healthy controls were evaluated for their apelin, adiponectin and high sensitivity C-reactive protein (hsCRP) levels, and homeostasis model assessment (HOMA) indexes. Plasma apelin-12 and adiponectin were determined by ELISA and RIA, respectively. Plasma apelin levels were lower in patients with elevated LDL-cholesterol compared to healthy controls (p<0.001). Plasma adiponectin concentration was also lower in the dyslipidemic patients (p<0.001). hsCRP levels were similar in the two groups. Fasting plasma glucose was normal in both groups. HOMA indexes in the dyslipidemic group were higher than the controls (p=0.005). A mild to moderate negative correlation with HOMA and positive correlation with high density lipoprotein cholesterol of apelin was found in the dyslipidemic group. Plasma apelin is decreased in non-obese, non-diabetic and normotensive patients with elevated LDL-cholesterol. Low apelin levels in hypercholesterolemia seem associated with insulin resistance, which needs to be investigated in larger populations as well as in other atherosclerotic conditions.Experimental and Clinical Endocrinology & Diabetes 08/2007; 115(7):428-32. · 1.56 Impact Factor