Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-converting enzyme-2 (ACE2) is the first human homologue of ACE to be described. ACE2 is a type I integral membrane protein which functions as a carboxypeptidase, cleaving a single hydrophobic/basic residue from the C-terminus of its substrates. ACE2 efficiently hydrolyses the potent vasoconstrictor angiotensin II to angiotensin (1-7). It is a consequence of this action that ACE2 participates in the renin-angiotensin system. However, ACE2 also hydrolyses dynorphin A (1-13), apelin-13 and des-Arg(9) bradykinin. The role of ACE2 in these peptide systems has yet to be revealed. A physiological role for ACE2 has been implicated in hypertension, cardiac function, heart function and diabetes, and as a receptor of the severe acute respiratory syndrome coronavirus. This paper reviews the biochemistry of ACE2 and discusses key findings such as the elucidation of crystal structures for ACE2 and testicular ACE and the development of ACE2 inhibitors that have now provided a basis for future research on this enzyme.
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PMID:Angiotensin-converting enzyme-2: a molecular and cellular perspective. 1554 71

Recent studies suggest that adipose tissue hormones ("adipokines") are involved in the pathogenesis of various complications of obesity, including hyperlipidemia, diabetes mellitus, arterial hypertension, atherosclerosis, and heart failure. Apelin and visfatin are two recently described adipokines, although they are also synthesized outside adipose tissue. Apelin exists in at least three forms, consisting of 13, 17, or 36 amino acids, all originating from a common 77-amino-acid precursor. In the cardiovascular system, apelin elicits endothelium-dependent, nitric oxide-mediated vasorelaxation and reduces arterial blood pressure. In addition, apelin demonstrates potent and long-lasting positive inotropic activity which is preserved even in injured myocardium and is not accompanied by myocardial hypertrophy. Apelin synthesis in adipocytes is stimulated by insulin, and plasma apelin level markedly increases in obesity associated with insulin resistance and hyperinsulinemia. In addition to regulating cardiovascular function, apelin inhibits water intake and vasopressin production. Visfatin, previously recognized as a pre-B cell colony-enhancing factor (PBEF), is abundantly expressed in visceral adipose tissue and is upregulated in some, but not all, animal models of obesity. Preliminary studies suggest that plasma visfatin concentration is also increased in humans with abdominal obesity and/or type 2 diabetes mellitus. Visfatin binds to the insulin receptor at a site distinct from insulin and exerts hypoglycemic effect by reducing glucose release from hepatocytes and stimulating glucose utilization in peripheral tissues. Thus, apelin and visfatin are unique among adipose tissue hormones in that they are upregulated in the obese state and both exert primarily beneficial effects.
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PMID:Apelin and visfatin: unique "beneficial" adipokines upregulated in obesity? 1694 Sep 39

Gravidas with obesity and diabetes ("diabesity") may transmit this syndrome to their children through genetic and nongenetic mechanisms. Here, we used the Lepr(db/+) diabese mouse to examine the magnitude of these transmission modes, focusing on adipose tissue (AT). We compared the following six groups: wild-type (+/+) offspring from +/+ or db/+ dams (different early life environment) and db/+ offspring from db/+ dams, fed a standard or high-fat diet. Weight gain (0-8 wk) was higher in +/+ offspring from db/+ vs. +/+ mothers, and even higher in db/+ vs. +/+ offspring from db/+ mothers. In addition, we observed a stepwise increase in AT and adipocyte size in +/+ from +/+ mice, +/+ from db/+ mice, and db/+ mice at 8 wk. Differences in weight and adiposity between +/+ offspring from db/+ vs. +/+ dams were more pronounced in males than in females. Leptin and apelin mRNA levels in white and brown AT were higher in +/+ offspring from db/+ vs. +/+ dams; however, leptin, apelin, and tumor necrosis factor-alpha expression were boosted more robustly in db/+ offspring. The high-fat diet amplified AT differences between db/+ vs. +/+ offspring from db/+ dams, but not between +/+ offspring from db/+ vs. +/+ dams. Moreover, db/+ but not +/+ offspring from db/+ mothers were insulin-resistant and hyperinsulinemic after a glucose challenge. In conclusion, the genetic transmission of the diabesity phenotype clearly prevailed, but the early-life diabesity environment had discernible effects on postnatal weight gain as well as on adipocyte size and adipokine expression at a postpubertal age.
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PMID:Adipose tissue in offspring of Lepr(db/+) mice: early-life environment vs. genotype. 1695 32

Visfatin and apelin are two novel adipocyte- secreted hormone proposed to link obesity with insulin resistance. In this study we investigated whether plasma visfatin and apelin levels were altered in normal, impaired glucose tolerance, and type 2 diabetic subjects. We also assessed the association between plasma visfatin, or apelin and body composition, metabolic parameters, and resistin concentrations in these subjects. The visfatin levels of fasting and 2-h post-glucose load were found to be significantly decreased in diabetics compared with the controls ( P<0.05). In contrast, basal apelin levels were significantly increased in the IGT and diabetic subjects compared with the controls ( P<0.05 and P<0.01). The apelin levels of 2-h post-glucose load were significantly higher than the basal levels in every group (all P<0.05). Fasting plasma visfatin was found to correlate positively and significantly with BMI, WHR, and fasting plasma resistin, but negatively with HbA1c and 2 h OGTT glucose. Multiple regression analysis showed that WHR, HbA1c, 2 h OGTT glucose were independent related factors influencing plasma visfatin levels. Fasting plasma apelin levels correlated positively with HOMA-IR, BMI, TC, LDL-C, FBG and Fasting plasma insulin. Multiple regression analysis also showed that HOMA-IR, BMI, and TC were independent related factors influencing plasma apelin levels. The present work indicates the potential link of visfatin and apelin with the pathogenesis of insulin resistance and T2DM.
Exp Clin Endocrinol Diabetes 2006 Nov
PMID:Changes and relations of circulating visfatin, apelin, and resistin levels in normal, impaired glucose tolerance, and type 2 diabetic subjects. 1717 35

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.
Exp Clin Endocrinol Diabetes 2007 Jul
PMID:Plasma apelin is lower in patients with elevated LDL-cholesterol. 2181 63

Apelin, a newly identified angiotensin (Ang) II homologue, has been implicated in diabetes. We previously reported that apelin exerts an opposing influence on the Ang II signaling. Our aim was to further implore whether apelin could regulate intrarenal artery tone in response to Ang II and Ang IV in diabetes. A Multi Myograph system was used to determine the isometric renal artery tone in diabetic db/db and control db/m+ mice. The phosphorylation, and protein levels of endothelial nitric oxide (NO) synthase (eNOS), and apelin receptor APJ were analyzed by Western blotting. Diminished expression of APJ protein and enhanced contractile responses to Ang II and Ang IV were exhibited in renal arteries from db/db mice. Apelin supplement reversed the abnormal renal vascular responsiveness to Ang II and acetylcholine, but not to Ang IV in db/db mice. Finally, in db/db mice, significant increases in phosphorylation of eNOS on serine 1177 and in NO generation were found in renal arteries pretreated with apelin. Our findings provide novel evidence for the regulatory roles of renal apelin system in vascular functions in diabetes. Apelin treatment may regulate the balance between Ang II and NO and thereby exert beneficial effects on the diabetic vascular pathophysiology.
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PMID:The novel peptide apelin regulates intrarenal artery tone in diabetic mice. 1769 36

Normal energy homeostasis requires a balance between fat storage and energy utilization that is guaranteed by regulation of one billion fat cells which arguably constitute the body's largest endocrine unit. Such physiology is required to maintain normal adiposity which if depleted from under- or malnutrition results in lipodystrophy that causes hormonal, reproductive, and developmental abnormalities. Conversely, excess adiposity provides inflammatory secretagogues, particularly from central visceral fat depots that enhance insulin resistance, excessive fatty acids with lipotoxicity and hypertension that escalate atherosclerosis including coronary artery disease. This review describes normal adiposity for maintenance of normal body mass and the roles of adipocyte hormones and adipokines for normal regulation of energy storage and its utilization. Therefore, in this context, the roles of leptin, insulin, adiponectin, and lesser known acylation-stimulating protein, visfatin, and apelin are outlined. Further, adipocyte inflammatory secretagogues are outlined that affect diabetes mellitus 2 with insulin resistance,fatty acid lipotoxicity, dyslipidemia, and hypertension that contribute to the metabolic syndrome. These effects are opposed by adipocyte hormones adiponectin, acylation-stimulating protein, visfatin, and apelin that help maintain normal energy utilization.
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PMID:The physiology of adiposity. 1839 31

Apelin is a recently discovered peptide, identified as an endogenous ligand of receptor APJ. Apelin and receptor APJ are expressed in a wide variety of tissues including heart, brain, kidneys and lungs. Their interaction may have relevant pathophysiologic effects in those tissues. In fact, the last decade has been rich in illustrating the possible roles played by apelin in human physiology, namely as a regulating peptide of cardiovascular, hypothalamus-hypophysis, gastrointestinal, and immune systems. The possible involvement of apelin in the pathogenesis of high prevalence conditions and comorbidities - such as hypertension, heart failure, and Diabetes Mellitus Type 2 (T2DM) - rank it as a likely therapeutic target to be investigated in the future. The present paper is an overview of apelin physiologic effects and presents the possible role played by this peptide in the pathogenesis of a number of conditions as well as the therapeutic implications that might, therefore, be investigated.
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PMID:The apelinergic system: the role played in human physiology and pathology and potential therapeutic applications. 1851 6

Apelin, a newly discovered adipocytokine produced by white adipose tissue, is also expressed in kidney and heart. It has been reported that apelin is related to echocardiographic features in hemodialyzed patients. Cardiovascular disease is a major contributor to the mortality and morbidity among patients with chronic renal failure as well as kidney allograft recipients. The aim of this study was to assess the association between apelin and coronary artery disease (CAD) among kidney allograft recipients. We investigated plasma apelin levels in 100 clinically stable, kidney allograft recipients with versus without CAD. We also assessed markers of endothelial cell injury-von Villebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), and CD146; markers of inflammation-high-sensitivity-reactive protein (hsCRP); other hemostatic parameters-tissue plasminogen activator (tPA) and its inhibitor (PAI-1); as well as other adipocytokines-adiponectin and resistin-using commercially available kits. Markers of endothelial dysfunction and inflammation were significantly elevated among patients with CAD levels, as well as with CAD or diabetes, compared with those without CAD. Apelin was significantly lower among patients with CAD, but higher in diabetic patients. Apelin content was similar in hypertensive versus normotensive kidney allograft recipients. We observed significant correlations between apelin and ICAM, resistin, adiponectin, calcium, phosphate, alanine and aspartate aminotransferase levels, with CAD or diabetes. Upon multiple regression analysis as well as CAD, adiponectin, and ICAM were predictors of apelin. Apelin was significantly reduced in kidney allograft recipients with CAD; its level was predicted by the presence of CAD, endothelial damage, or inflammation. Apelin and other adipocytokines may be associated with inflammation and its clinical consequences.
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PMID:Apelin, a novel adipocytokine, in relation to endothelial function and inflammation in kidney allograft recipients. 1910 Apr 14

Oxidative stress is thought to be one of the underlying mechanisms of diabetic microvascular complications such as diabetic nephropathy and diabetic retinopathy (DRP). Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthase inhibitor and increased by oxidative stress. Apelin is an endogenous ligand for human orphan G-protein-coupled receptor, APJ and increases NO generation. In this study, our aim was to evaluate ADMA and apelin levels in diabetic patients with or without retinopathy and their relationships between retinopathy stages and metabolic parameters. Seventy-nine diabetic patients were included into the study and classified into three groups. Group 1 consisted of 41 patients with no DRP (NDRP), group 2 consisted of 23 patients with nonproliferative DRP (NPDRP), and group 3 consisted of 15 patients with proliferative DRP (PDRP). Plasma ADMA and apelin levels were found to be similar in all groups. But, there was a positive correlation between apelin levels and urinary albumin/creatinine ratio. Further studies involving larger patients populations and healthy controls should be done to clarify the pathogenetic significance of ADMA and apelin in diabetic microvascular complications.
Diabetes Res Clin Pract 2009 Jun
PMID:Plasma apelin and asymmetric dimethylarginine levels in type 2 diabetic patients with diabetic retinopathy. 1976 42


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