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)

Natriuretic peptides (ANP, BNP and CNP) comprise a family of structurally related peptides, which are derived from three different genes and which share a 17-amino acid internal ring. Besides their peripheral involvement in diuresis and blood pressure regulation these peptides, their bioactive fragments and their corresponding receptors (natriuretic peptide receptors NPR-A, NPR-B and NPR-C) are found throughout the central nervous system (CNS): NPR-A and NPR-C are found on neurons and astrocytes, while NPR-B is located mainly on neurons and partially colocalizes with NPR-A. In the CNS of man and rodents NPR-A is found mainly in cortex and hippocampus, whereas NPR-B is present in the amygdala and several brainstem regulatory sites. NPR-C is found widely within the CNS i.e. in neocortex, limbic cortex, the hippocampal area and the amygdala. These peptides and their receptors represent an important neuromodulatory system within the CNS, which is involved not only in the regulation of fluid homeostasis but also directly influences emotional behaviour, such as anxiety and arousal, and the sequelae of stress hormone release and autonomic nervous system activation. Natriuretic peptides are specifically involved in the regulation of the hypothalamo-pituitary-adrenocortical (HPA) system: in man and rodents ANP inhibits the HPA system at all regulatory levels, while CNP stimulates the release of cortisol. Complementarily, the anatomic structure of natriuretic peptide systems within the CNS supports an important role for these in normal and pathologic emotional behaviour (e.g. anxiety and panic): in rodents ANP was found to reduce anxiety levels, whereas CNP induced the opposite effect. In patients with panic disorder basal ANP plasma levels are lower in comparison to healthy volunteers, but ANP secretion is faster and more pronounced during experimentally induced panic attacks. The inhibitory potency of ANP could explain the unexpected and so far unresolved failure of autonomic and HPA system activation during panic attacks. Moreover, panic anxiety and concomitant ACTH and cortisol secretion elicited by stimulation with the panicogen cholecystokinin-tetrapeptide were also attenuated by ANP infusions in patients as well as in healthy volunteers. Hence, it may be surmised that in man and rodents ANP reduces anxiety and terminates panic attacks and their neuroendocrine sequelae.
Exp Clin Endocrinol Diabetes 2000
PMID:Effects of natriuretic peptides upon hypothalamo-pituitary-adrenocortical system activity and anxiety behaviour. 1076 26

C-type natriuretic peptide (CNP), a recent addition to the family of natriuretic peptides including atrial and brain natriuretic peptide (ANP, BNP), is believed to be an endothelium-derived vasodilator and to have an antimitotic effect. ANP and BNP concentrations are increased in conditions such as congestive heart failure, but cardiac CNP concentrations have not been investigated in this connection. Diabetes mellitus also involves myocardial dysfunctions without coronary artery disease or systemic hypertension. We therefore investigated the cardiac expression of CNP mRNA compared with that of BNP mRNA in streptozotocin (STZ)-diabetic rats. STZ- diabetic male Wistar rats (n=6) were studied in comparison with controls (n=6). The animals were characterised by their mean arterial blood pressure and plasma glucose concentrations. After extraction of total cardiac RNA, a specific cDNA probe of BNP was used for northern blot analysis, whereas myocardial CNP expression was analysed by an RNase-protection assay. Twelve weeks after diabetes was induced, the rats were normotensive (96.4+/-2.0 compared with 95.1+/-1.9 mmHg) and hyperglycaemic (615+/-61 compared with 165+/-21 mg/dl; P<0.001). Left ventricular pressure was significantly impaired (76.8+/-6.4 compared with 51.2+/-3.6 mmHg). STZ-diabetic rats had a 3.2-fold increase in cardiac BNP expression compared with controls. In contrast, cardiac CNP mRNA concentrations were decreased 2.6-fold. CNP seems to be downregulated like other peptides with antimitotic and vasodilator activities (nitric oxide, prostacyclin, kinins). This may contribute to cardiac dysfunction in diabetes mellitus and suggests that stimulation of CNP expression could provide cardiac protection in such cases.
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PMID:Opposite regulation of brain and C-type natriuretic peptides in the streptozotocin-diabetic cardiopathy. 1082 32

Monitoring of 24-hour ambulatory blood pressure(ABPM), measurements of circulating vasoactive substances and microalbuminuria, and assessment of gene polymorphisms as genetic markers are introduced to detect and evaluate hypertension. Classifications of ABPM based on impact on risks of cardiovascular diseases have been currently available. Plasma level of brain natriuretic peptide(BNP), a cardiac hormone, increases markedly in congestive heart failure, in proportion to its severity, and is evaluated as a potential index of severity of heart failure. In addition, serum level of hepatocyte growth factor(HGF), a member of endothelium specific growth factors, in hypertension might be useful for evaluating the presence of complications and degree of endothelial dysfunction. In diabetes mellitus, onset of microalbuminuria appeared as an important sign of early nephropathy. There is growing evidence that microalbuminuria is an independent predictor of atherosclerosis and premature death in the general population. Current studies have shown that gene polymorphisms including components of the renin-angiotensin-aldosterone system may be possible genetic markers for hypertension and its associated cardiovascular diseases. Our data suggest positive linkages between hypertension and 4 gene polymorphisms including angiotensinogen Met235Thr, angiotensin converting enzyme I/D, aldosterone synthase CYP11B2 T-344C, and endothelial nitric oxide synthase Glu298Asp in the Aomori population.
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PMID:[New techniques and laboratory examinations in the detection and evaluation of hypertension]. 1130 25

Mesangial cells from nonobese diabetic (NOD) mice (D-NOD) that develop diabetes at 2-4 mo express an increased density of atrial natriuretic peptide (ANP) clearance receptors [natriuretic peptide C receptor (NPR-C)] and produce less GMP in response to ANP than their nondiabetic counterparts (ND-NOD). Our purpose was to investigate how both phenotypic characteristics were regulated. Epidermal growth factor (EGF) and heparin-binding (HB)-EGF, but not platelet-derived growth factor or insulin-like growth factor I, inhibited (125)I-ANP binding to ND-NOD and D-NOD mesangial cells, particularly in the latter. NPR-C density decreased with no change in the apparent dissociation constant, and there was also a decrease in NPR-C mRNA expression. The EGF effect depended on activation of its receptor tyrosine kinase but not on that of protein kinase C, mitogen-activated protein kinases, or phosphoinositide-3 kinase. Activation of activator protein-1 (AP-1) was necessary, as shown by the inhibitory effect of curcumin and the results of the gel-shift assay. The cGMP response to physiological concentrations of ANP was greater in EGF-treated D-NOD cells. These studies suggest that EGF potentiates the ANP glomerular effects in diabetes by inhibition of its degradation by mesangial NPR-C via a mechanism involving AP-1.
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PMID:Regulation of ANP clearance receptors by EGF in mesangial cells from NOD mice. 1145 15

Omapatrilat was designed to inhibit simultaneously angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The ubiquitous involvement of the renin-angiotensin-aldosterone system, originally conceived as an axis of sodium and fluid metabolism in inflammation, thrombosis and cardiac and smooth muscle hypertrophy, is a major factor in disease progression for conditions as diverse as hypertension, heart failure, coronary artery disease and diabetes. Interruption of angiotensin II generation and bradykinin degradation by ACE inhibition is a major therapeutic advance in the management of these diseases. NEP metabolizes both bradykinin and the natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide, c-type natriuretic peptide and adrenomedullin). These peptides counter the adverse effects of angiotensin II by their vasodilator, natriuretic, diuretic and autonomic neural actions; by their antitrophic effects; and by suppressing plasma renin activity. These two systems can be considered key components of a cardiorenal axis that maintains blood pressure and cardiopulmonary blood volume within a stable range. This balance is compromised in the setting of heart failure and primary hypertension. The combination of ACE and NEP inhibition should augment the beneficial hemodynamic and tissue effects of bradykinin and the natriuretic peptides. Vasopeptidase inhibition, therefore, is a novel approach to cardiovascular therapy, with implications for hypertension, heart failure, renal function and ischemic heart disease.
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PMID:Vasopeptidase inhibition: a novel approach to cardiovascular therapy. 1187 87

Diastolic heart failure is defined clinically when signs and symptoms of heart failure are present in the presence of preserved left ventricular systolic function (ejection fraction >45%). The incidence and prevalence of primary diastolic heart failure increases with age and it may be as high as 50% in the elderly. Age, female gender, hypertension, coronary artery disease, diabetes, and increased body mass index are risk factors for diastolic heart failure. Hemodynamic consequences such as increased pulmonary venous pressure, post-capillary pulmonary hypertension, and secondary right heart failure as well as decreased cardiac output are similar to those of systolic left ventricular failure, although the nature of primary left ventricular dysfunction is different. Diagnosis of primary diastolic heart failure depends on the presence of preserved left ventricular ejection fraction. Assessment of diastolic dysfunction is preferable but not mandatory. It is to be noted that increased levels of B-type natriuretic peptide does not distinguish between diastolic and systolic heart failure. Echocardiographic studies are recommended to exclude hypertrophic cardiomyopathy, infiltrative heart disease, primary valvular heart disease, and constrictive pericarditis. Myocardial stress imaging is frequently required to exclude ischemic heart disease. The prognosis of diastolic heart failure is variable; it is related to age, severity of heart failure, and associated comorbid diseases such as coronary artery disease. The prognosis of severe diastolic heart failure is similar to that of systolic heart failure. However, cautious use of diuretics and/or nitrates may cause hypotension and low output state. Heart rate control is essential to improving ventricular filling. Pharmacologic agents such as angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers are used in selected patients to decrease left ventricular hypertrophy. To decrease myocardial fibrosis, aldosterone antagonists have a potential therapeutic role. However, prospective controlled studies will be required to establish their efficacy in primary diastolic heart failure.
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PMID:Primary diastolic heart failure. 1198 32

To clarify the relationship of the plasma brain natriuretic peptide (BNP) levels to diabetic complications, we studied plasma BNP levels in 100 normotensive diabetic patients without clinical cardiac disease and macroalbuminuria. The values of plasma BNP levels were not significantly different between patients with microalbuminuria and those with normoalbuminuria (12.2 +/- 2.0 vs. 12.3 +/- 1.3 pg/ml, means +/- S.E.M.), and neither were the BNP levels of patients with and without retinopathy significantly different (15.7 +/- 3.4 vs. 11.4 +/- 1.0 pg/ml). BNP levels of the subjects with cerebral vascular disease (CVD) were not statistically different from those of subjects without CVD (17.5 +/- 5.5 vs. 11.7 +/- 1.0 pg/ml), although mean BNP value of subjects with CVD was higher than that of subjects without it. With regard to peripheral vascular disease (PVD), BNP levels of the subjects with PVD were not statistically different from those of subjects without PVD (13.5 +/- 2.3 vs. 12.1 +/- 1.2 pg/ml). We also studied radial arterial oxygen tension of 45 patients and compared these levels between those with and without diabetic complications. However, we could not find statistical differences between them. In conclusion, our study suggests that BNP and arterial oxygen tension levels will not be affected by retinopathy, microalbuminuria, CVD, and PVD in normotensive diabetic patients without clinical cardiac disease and macroalbuminuria. Therefore, when normotensive diabetic patients without macroalbuminuria show increased plasma level of BNP, we should examine their cardiac function in detail, considering subclinical cardiac disease.
J Diabetes Complications
PMID:Plasma brain natriuretic peptide levels in normotensive Type 2 diabetic patients without cardiac disease and macroalbuminuria. 1201 90

Brain natriuretic peptide (BNP) is produced in cardiac myocytes, and increased secretion is closely associated with cardiac dysfunction. However, several fundamental aspects of BNP expression in the myocardium have not yet been resolved. In the present study, we report the presence of a precursor BNP mRNA transcript and a mature BNP mRNA transcript in normal porcine hearts. In normal pigs, the amount of precursor BNP mRNA was similar in atrial and ventricular myocardium, whereas the mature BNP transcript was 10- to 50-fold more abundant in atrial than in ventricular myocardium. Quantitation of proBNP in normal porcine hearts by radioimmunoassay disclosed abundant proBNP in the atria, whereas proBNP was undetectable in the ventricles. Laser confocal microscopy revealed proBNP in secretory granules of atrial but not in the ventricular myocardium of normal pigs. Mild streptozotocin-induced diabetes doubled the expression of BNP mRNA in porcine atrial myocardium (P=0.03), but was without effect on BNP mRNA in the ventricular myocardium. The data suggest that BNP mRNA processing and proBNP storage differ between the atrial and ventricular myocardium. The results also imply that diabetes increases cardiac BNP expression in a chamber-dependent manner.
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PMID:Chamber-dependent expression of brain natriuretic peptide and its mRNA in normal and diabetic pig heart. 1210 38

Assays for natriuretic peptides have received considerable attention as potential screening tests for congestive heart failure and left ventricular dysfunction. However, information regarding the impact of age, sex, and other physiologic characteristics on natriuretic peptide levels is limited. We examined a healthy reference sample of 911 subjects (mean age 55 years, 62% women) from the Framingham Heart Study who were free of hypertension, valvular disease, diabetes, atrial fibrillation, obesity, coronary heart disease, congestive heart failure, and renal failure, and who had normal left ventricular systolic function. Plasma brain natriuretic peptide and N-terminal atrial natriuretic peptide levels were measured, and multivariable regression used to assess correlates of natriuretic peptide levels. The strongest predictors of higher natriuretic peptide levels were older age and female sex. Other multivariable predictors included lower diastolic blood pressure (higher pulse pressure), lower body mass index, and higher left atrial size. Reference limits were then formulated based on the empirical distribution of natriuretic peptide levels by gender both across all ages and partitioned by age. Age-pooled reference limits compared with age-specific limits classified a higher proportion of healthy elderly subjects (17% vs 2.5%), but a lower proportion of healthy young subjects (1% vs 2.5%) as "abnormal." We conclude that interpretation of natriuretic peptide levels should take into consideration gender and possibly age. The reference limits derived from this large, healthy community-based sample will aid in the identification of elevated natriuretic peptide levels in clinical practice.
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PMID:Impact of age and sex on plasma natriuretic peptide levels in healthy adults. 1212 13

Congestive heart failure poses significant challenges to physicians with both diagnosis and management. B-type natriuretic peptide (BNP) is synthesized in the cardiac ventricles. It correlates with ventricular function, NYHA classification, and prognosis. It is extremely useful in the emergency department in patients presenting with acute dyspnea. It has a particularly strong negative predictive value. In addition, it should be important in screening patients for heart diease, either for those who are at high risk (chemotherapy, diabetes) or as a possible screen before echocardiography. In the future, BNP may be used to modulate treatment of patients in the decompensated setting as well as in titrating outpatient therapy.
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PMID:The impact of B-type natriuretic peptide levels on the diagnoses and management of congestive heart failure. 1215 66


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