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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the past decade there have been considerable advances in basic knowledge of the renin-angiotensin system (RAS). The most important new development has been the appreciation of a tissue based RAS that can be independently regulated from the renal and vascular RAS. Greater insight into the mechanism by which angiotension-II (AII) exerts its action has been achieved through the study of molecular biology and pharmacological characterization of multiple receptor subtypes. This review summarises the features and distribution of several binding subtypes that may mediate the diverse functions of AII. Of these AT1 subtype is the most well known receptor which preferentially binds AII and AIII. The AT1 receptor site appears to mediate the classic angiotensin responses concerned with the body water balance and the maintenance of blood pressure. Less is known about the AT2 sites which also bind AII and AIII and may play a role in vascular growth. Recently, an AT3 has been discovered in cultured neuroblastoma cells and an AT4 site which preferentially binds AIV. It has been implicated in memory aquisition and retrieval and in the regulation of blood flow. Another important aspect covered is the primary and secondary messengers involved during the signal transduction after the binding of AII with receptors. A stress has also been given on the regulation of density and affinity of AII receptors by various physiological parametres as they affect the responses of RAS. Autoregulation by RAS, salt intake, development and aging and some of the hormones are important variables which could affect the AII receptors. Interactions of AII with various neuroeffector transmission involved in the regulation of water-electrolyte balance and BP regulation play an important role in the maintenance of the homeostasis. AII has been suggested to increase the NAergic transmission by enhancing synthesis, release, inhibiting reuptake by the presynaptic nerve terminals as well as enhancing cell responsiveness to the transmitter. The finding of existence of AII receptors in vagal afferent nerve terminals suggests that its baroreflex inhibitory effect is mediated by inhibiting neurotransmitter release at NTS in the baroreflex arc. Moreover, AII acts on the central receptors to stimulate AVP and ACTH secretion, drinking and peripherally increase synthesis and secretion of aldosterone. Interactions of RAS with kallikrein-kinin system and prostaglandins strongly support the existence of a balance between renal depressor and pressor substances. AII is now considered a growth promotor in cardiovascular tissues and the resultant vascular hypertrophy could contribute in the maintenance of hypertension. AII also plays a role in the kidney, not only as a regulator of hemodynamics but also in the structural changes occurring in a variety of renal disorders. In addition to the more well studied functions of RAS in RVH the review also highlights the potential contribution by the RAS to other clinically relevant syndromes such as aortoarterities induced RVH, hyperaldosteronism, heavy metal induced cardiovascular effects, diabetes mellitus and thyroid dysfunction. Although the receptor subtypes involved in these pathological states have not been definitely identified, research efforts in this direction are ongoing.
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PMID:Angiotensin II--receptor subtypes characterization and pathophysiological implications. 864 21

A number of endocrine disorders are associated with varying degrees of glucose intolerance. Sustained hypersecretion of hormones with actions antagonistic to insulin (e.g., GH, glucocorticoidos, catecholamines, glucagon) or which interfere with insulin secretion (e.g., catecholamines, hypokalemia) is often associated. And so, acromegaly, Cushing's syndrome, pheochromocytoma, primary aldosteronism, hyperthyroidism, glucagonoma and others are included in endocrine-associated diabetes. The glucose intolerance occurring secondary to endocrine disorders is usually moderate degree and overt diabetes with symptomatic hyperglycemia is an uncommon event, unless an underlying genetic diabetic diathesis also present in the same individual. The small subgroup of acromegalics(5-10%) with severe glucose intolerance requiring insulin therapy have low endogenous insulin levels and insulin responses that are markedly impaired. It has been suggested that these patients are really true diabetics. These are patients with NIDDM. Retinal, renal and neurological complications are uncommon in patients with endocrine-associated diabetes.
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PMID:[Diabetes secondary to endocrinolopathies]. 891 32

Blood pressure responses to increases and decreases in dietary salt intake are heterogeneous. In some hypertensive individuals, decreases in blood pressure with salt restriction are clinically significant and approach that achieved with medication. In others, little or no change in blood pressure occurs, whereas in still others, blood pressure may actually increase with salt restriction. The heterogeneous responses are partly acquired and involve the influences of age, the intake of other electrolytes, and the influence of certain medications. Genetic predisposition may also play a substantial role because salt sensitivity is increased in black individuals and in persons with non-insulin-dependent diabetes mellitus. Some uncommon but readily diagnosed salt-sensitive genetic syndromes, such as glucocorticoid-remediable aldosteronism and Liddle syndrome, have been identified. Short-term volume expansion and contraction and longer-term dietary interventions appear to be reproducible and may be used to identify salt-sensitive and salt-resistant individuals; however, these maneuvers are cumbersome and cannot be used on a large scale. Molecular genetic techniques for identifying individuals with salt-sensitive and salt-resistant essential hypertension are not yet available, but if the putative gene polymorphisms are identified, such techniques may replace the current trial-and-error methods.
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PMID:Heterogeneous responses to changes in dietary salt intake: the salt-sensitivity paradigm. 902 56

Two distinct subtypes of patients with primary aldosteronism due to aldosterone-producing adenomas (APA), based on different aldosterone responses to angiotensin, have been identified. We evaluated the relationship between adrenal zona fasciculata-like histotype and response of plasma aldosterone to upright posture in a series of patients with APA. Twenty-five patients were retrospectively divided in two groups according to aldosterone response to posture, i.e., a first group without postural change of aldosterone (n = 19) and a second group with at least 30% aldosterone increase after standing (n = 6). The percentage of zona fasciculata-like cells was calculated at histology in all adenoma tissues removed at adrenalectomy. The two groups of patients were similar in sex, age, systolic/diastolic blood pressure, supine/upright plasma renin activity, supine/upright aldosterone, tumor size. No differences between the two groups were observed as to zona fasciculata-like (84 +/- 3% vs 71 +/- 9%, P NS) and non-zona fasciculata-like cells percentage in adenoma tissues. No inverse correlation was found in either group between the percentage change from supine to upright aldosterone and the percentage of zona fasciculata-like cells. Aldosterone and cortisol responses to ACTH testing were similar in the two groups. Our results indicate that the two subtypes of primary aldosteronism based on different postural responses of aldosterone are not due to a different prevalence of zona fasciculata-like histotype in APA.
Exp Clin Endocrinol Diabetes 1998
PMID:Zona fasciculata-like histotype and aldosterone response to upright posture are not related in aldosterone-producing adenomas. 951 64

The relationship between arterial hypertension and insulin resistance has long been established. We used primary hyperaldosteronism as a model of the relationship between secondary hypertension and insulin sensitivity. Our group consisted of 9 patients with arterial hypertension caused by primary hyperaldosteronism. Five of these patients with aldosterone producing adenoma were operated on and four patients with idiopathic hyperaldosteronism were treated with spironolactone. Hyperinsulinaemic euglycaemic clamp technique was performed before and at least 6 months following the treatment to evaluate the insulin action. Significantly lower glucose disposal rate (M), insulin sensitivity index (M/I) and decreased metabolic clearance rate of glucose (MCR(G)) were found in patients before treatment as compared to healthy controls. In both treated groups the blood pressure and plasma potassium concentrations returned to normal values, whereas plasma aldosterone levels were normalised only after surgical removal of the adenoma. Significantly improved insulin action (M/I: 30.2 +/- 5.9 vs. 51.4 +/-12.2 micromol.kg(-1).min(-1) per mU.l(-1) x 100, p = 0.017) was observed in patients after operation of aldosterone producing adenoma. In contrast, spironolactone treatment of patients with idiopathic hyperaldosteronism did not significantly influence insulin action (M/I: 24.5 +/- 7.3 vs. 18.7 +/- 7.6 micromol.kg(-1).min(-1) per mU.l(-1) x 100, p = 0.198). Since plasma aldosterone concentrations have been normalised only in patients after removal of the adenoma whereas they remained increased in spironolactone treated group, we suppose that aldosterone itself could play a role in the development of impaired insulin action.
Exp Clin Endocrinol Diabetes 2000
PMID:Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment. 1076 28

Three patients with functional adrenal tumors, Cushing's syndrome, primary aldosteronism and pheochromocytoma, who underwent adrenalectomy and were subsequently cured, were studied. All these patients had been treated for diabetes for several years before the diagnosis of adrenal tumors. In each case the state of diabetes before and after surgery, including parameters of insulin secretion and insulin resistance, was compared to demonstrate how the adrenal disorder influenced the nature of diabetes. In the case of Cushing's syndrome the hypercortisolemia caused insulin resistance in the peripheral tissues. In the case of primary aldosteronism, excessive production of aldosterone diminished insulin secretion possibly through hypokalemia. Pheochromocytoma affected both insulin secretion and insulin sensitivity through hypersecretion of catecholamines. In all these patients the adrenal tumors were found in clinical contexts other than management of diabetes itself. By careful retrospective review of these three patients' history, several important points that might have drawn the physician's attention to the underlying adrenal disorders were pointed out. These included past history of acute myocardial infarction with onset at unexpectedly young age in the case of Cushing's syndrome and unexpectedly high insulin resistance for the patient's body mass index in the case of pheochromocytoma.
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PMID:Three patients with adrenal tumors having been treated simply for diabetes mellitus. 1091 24

The authors analyse hormonal and morphological characteristics of adrenal incidentalomas, i.e. pathological adrenal masses accidentally found on CT scan performed due to extraadrenal causes of other causes of adrenal pathology. The group of patients was consisted by 42 patients at the age 24-79 years (27 females and 15 males). The most frequent clinical symptoms included arterial hypertension, diabetes mellitus and obesity. CT examinations revealed 36 cases of unilateral lesions (in 21 cases the lesions were localised on the right and in 15 cases on the left) and 6 bilateral lesions. The size of adrenal masses ranged from 7 mm to 12 cm. The CT examination helped in characterising myelolipomas in 3 cases, cysts in two cases, and pre-assuming malignity in 6 cases. Hormonal analyses have revealed primary aldosteronism in 2 cases, subclinical hypercortisolism in 1, steroid enzymopathy in 2 and secondary hyperaldosteronism in 2 patients. No patient had catecholamine overproduction. 19 patients were indicated for adrenalectomy with the following histological findings.: adenoma (n = 5), cyst (n = 2), myelolipoma (n = 3), carcinoma (n = 3), feochromocytoma, ganglioneuroma, metastases, lymphoma, sarcoidosis and pseudodrenal structure--Gravitz tumor (n = 1, respectively). The size of all neoplasms exceeded 3 cm, therefore the authors recommend adrenalectomy in incidentalomas with hormonal activity exceeding 3 cm in size. (Tab. 2, Fig. 1, Ref. 17.)
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PMID:[Hormonal and morphologic characteristics of adrenal incidentalomas]. 1118 53

The ratio of serum aldosterone to plasma renin activity (PRA) has been proposed as sensitive screening method in the diagnosis of primary aldosteronism under random conditions. However, the method for determination of renin activity is hampered by the necessity of ice cooling during storage and transport. The present study was therefore conducted to examine the ratio of serum aldosterone to plasma renin concentration (ARR) and its usefulness in diagnosis of primary aldosteronism under ambulatory conditions and given antihypertensive medication. 146 patients with arterial hypertension who consecutively attended the outpatient clinic were studied prospectively. Patients with secondary hypertension besides primary aldosteronism were not included in the series. 37 normotensive patients served as control. Also, 17 patients with known primary aldosteronism were retrospectively examined. Among the hypertensive group 2 patients with Conn's syndrome were newly detected (1.4%). ARR was 7.92 +/- 6.04 [pg/ml]/[pg/ml] in normotensive controls (range from 2.03 to 26.98), 14.61 +/- 18.50 [pg/ml]/[pg/ml] in patients with essential hypertension (n = 144, range from 0.41 to 115.45) and 155.92 +/- 127.84 [pg/ml]/[pg/ml] in patients with primary aldosteronism (n = 19, range from 6.75 to 515). 17 of the 19 patients with Conn's syndrome had an ARR of more than 50. Under ongoing drug treatment this represents a sensitivity of 89% and a specificity of 96%. Sensitivity decreased to 84% and specificity increased to 100% when a second criteria (aldosterone > or = 200 pg/ml) was included. In summary, ARR using renin concentration is a useful screening parameter for primary aldosteronism.
Exp Clin Endocrinol Diabetes 2002 Apr
PMID:Ratio of serum aldosterone to plasma renin concentration in essential hypertension and primary aldosteronism. 1192 71

There is an association of glucose intolerance and diabetes with primary aldosteronism, but the frequency and mechanisms are not clear. This paper reviews the possible mechanisms of impaired glucose metabolism in primary aldosteronism. Patients with primary aldosteronism can have impaired pancreatic insulin release and reduction in insulin sensitivity. These effects may be due to hypokalemia, but the evidence suggests other factors such as a direct impact of excess aldosterone on insulin action in contributing to the metabolic dysfunction. In general adrenal surgery in cases of aldosterone-producing adenoma will correct the metabolic abnormalities, but it is less sure if treatment with spironolactone in cases of idiopathic hyperplasia will correct impaired glucose tolerance.
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PMID:The effect of aldosterone on glucose metabolism. 1264 8

Primary hyperaldosteronism (PH) is frequently considered to be a secondary form of diabetes mellitus (DM). In our previous study we attempted to evaluate the prevalence of DM among patients with PH compared to control subjects with essential hypertension (EH). We have noted a relatively high prevalence of DM and impaired glucose tolerance in PH, but the differences between the PH and EH groups did not reach statistical significance. We performed this study to assess whether the effective treatment of PH (surgical and conservative) would improve the glucose tolerance. We have studied 24 patients with PH of the following two subtypes: aldosterone-producing adenoma (APA) treated with adrenalectomy and idiopathic hyperaldosteronism (IHA) treated with spironolactone. No significant changes of glucose levels were found in the 60th and 120th min of the oral glucose tolerance test (OGTT) in the APA group. On the other hand, fasting glucose levels were decreased significantly after adrenalectomy. Plasma glucose levels were significantly increased in the 60th min, but no differences were found in fasting values and in the 120th min in the IHA group. There was a significantly higher incidence of impaired glucose tolerance (36 per cent before, 45 per cent after treatment) and DM (9 per cent, 18 per cent) in the IHA group compared to the APA group (8 per cent, 32 per cent; DM 0 per cent, 0 per cent). In conclusion, the treatment of PH does not improve glucose tolerance. Mild worsening of glucose tolerance after treatment could be explained by an increase of the body mass index. These data, in accordance with our previous study, do not support the idea that PH is a secondary form of diabetes mellitus.
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PMID:Does the treatment of primary hyperaldosteronism influence glucose tolerance? 1289 64


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