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

1. Angiotensin II (AII) plays a major role in cardiovascular function via direct actions on the vasculature, kidney, adrenal, heart, brain and sympathetic nerves. The cellular effects of AII are extensive and encompass hypertrophy, hyperplasia and the deposition of extracellular matrix. 2. The actions of AII are mediated by the AT1 and AT2 membrane receptor subtypes, and additional forms of each subtype. Evidence is emerging that selective changes in AII receptor subtypes occur in cardiovascular diseases. 3. Thyroid dysfunction increased cardiac, liver and kidney AII receptor density but decreased adrenal gland receptor density. In the heart, there was a selective increase in AT2 receptor density. 4. Diabetes increased cardiac, liver and adrenal gland AII receptor densities but decreased kidney receptor density. 5. Hypertension increased AII receptor density in the heart and kidney. A corresponding increase in receptor mRNA was prevented by selective AT1 receptor antagonists. 6. The human heart contained AII receptors in all chambers; right atrial receptor density was increased in coronary artery bypass graft patients. 7. The presence of AII receptor changes in these models of cardiac hypertrophy and hypertension raises the possibility of using orally active, subtype-selective agonists and antagonists to treat particular forms of cardiovascular diseases.
 ...
PMID:Angiotensin receptors in cardiovascular diseases. 786 32

1. The combined effect of diabetes and hypertension on the plasma angiotensin II (AII)/glomerular AII receptor (AII-R) relationship in streptozotocin-induced diabetes was investigated as well as the effect of glycaemic control on this relationship. 2. Diabetes was induced in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with streptozotocin 60 mg/kg and blood sugars maintained between 18-21 mmol/L (uncontrolled diabetes) and 4-8 mmol/L (controlled diabetes). Rats were killed on days 1 and 7. Angiotensin II receptor was estimated by saturation analysis and plasma AII by radio-immunoassay. 3. Angiotensin II receptors were significantly higher in non-diabetic SHR than WKY rats (708 +/- 62 and 388 +/- 36 fmol/mg protein, respectively, P = 0.0008). Plasma AII were comparable in both groups (47 +/- 2.7, 38 +/- 3.5 pg/mL, respectively) and a significant inverse relationship between AII/AII-R was observed (WKY P = 0.02 and SHR P = 0.004). 4. On day 7, plasma AII and AII-R levels in diabetic groups were comparable with those of their non-diabetic controls. Diabetic WKY rats maintained an inverse correlation between AII and AII-R (controlled P = 0.04 and uncontrolled P = 0.015), but this did not occur in the SHR. 5. Absence of receptor response to varying ligand concentrations in the diabetic SHR may contribute to the development of nephropathy. Glycaemic control does not appear to reverse this abnormality in the SHR, so that co-existent hypertension may have a more direct influence on renal function.
 ...
PMID:Abnormality of the glomerular angiotensin II receptor in experimental diabetic nephropathy. 832 23

The mechanisms responsible for the abnormalities in the vascular wall associated with long standing diabetes mellitus are incompletely understood. The aim of this investigation was to assess the effects of angiotensin II and high glucose on the production of platelet-derived growth factor (PDGF) in human endothelial cells. For this purpose, a primary culture was obtained from fresh human umbilical cords by collagenase digestion of the vein interior. A high glucose medium increased the production of PDGF and a similar effect was observed by the addition of mannitol. These data are consistent with a stimulatory effect of glucose on PDGF that is mediated by the osmotic effect of this substance. Angiotensin II significantly increased PDGF in human endothelial cells and the effect was accompanied by a transient increase in cytosolic calcium. The angiotensin II-induced intracellular Ca2+ increases, PDGF production were completely abolished by saralasin and neomycin, respectively. We postulate that the increased production of PDGF by the vascular endothelium in response to high glucose and angiotensin II may participate in the development of the diabetic angiopathy.
 ...
PMID:Increased production of PDGF by angiotensin and high glucose in human vascular endothelium. 889 Sep 24

In this review paper, three aspects related to alteration in capillary permeability, based on a series of recent observations from this laboratory, are examined. Firstly, the determinants of capillary extravasation, which include pre- and post-capillary resistances in different microcirculation networks, as well as endothelial permeability per se, are described with particular reference to the heterogeneous character of both regulatory components, reported by this and other groups. Secondly, the endothelium-interstitium relationship, responsible in part for the maintenance of the interstitial compartment physicochemical characteristics, is introduced as an important factor in regulating the traffic of vital nutrients delivered to the cell mass, and the removal of waste products from the cellular compartment to the microcirculation, for ultimate excretion. Examined in this manner, it appears that modulation of capillary permeability is essential for the maintenance of cellular life, yet the neurohumoral mechanisms involved in the control of microcirculation networks are just starting to be identified. A number of morbid conditions characterized by multiorgan involvement exhibit a common pathophysiological denominator which involves endothelium-interstitium relationships, as illustrated in experimental animal models of arterial hypertension, diabetes mellitus, heart failure, and degenerative renal diseases. Enhanced capillary permeability associated with local interstitial edema in specific organs, such as the heart and the kidney, in arterial hypertension and diabetes mellitus, as well as decreased permeability in peripheral tissues, such as the skeletal muscle and the skin, in congenital cardiomyopathy, have been documented. It is likely that alteration in the characteristics of interstitial matrix composition contributes to target organ damage in these examples of systemic disorders from different etiologies. Thirdly, the recent identification of autocoids and hormones involved in the direct and indirect control of capillary permeability has led to the development of pharmacological tools capable of modulating pre- and post-capillary vascular tonus, as well as endothelial permeability. Angiotensin II antagonism, bradykinin B1-receptor inhibition, and modulation of eicosanoid production, in particular thromboxane A2, are associated in some of the above-described disorders, with normalization of capillary permeability defects, and occasionally with improvement in organ function. The eventual development of agents capable of directly controlling the physicochemical characteristics of the interstitial matrix should be of interest, not only for preventing the development of irreversible matrix structural alterations but also for facilitating the traffic of metabolites between capillaries and the cell mass of vital organs.
 ...
PMID:Consequences of alteration in capillary permeability. 894 69

As angiotensin-converting enzyme inhibition is accompanied by a marked decrease in glomerular protein loss, the hypothesis was tested that an increase of the glomerular transcapillary hydraulic pressure difference by exogenous angiotensin II would increase microalbuminuria in patients with insulin (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Acute effects of increasing doses of angiotensin II (1, 3 and 6 ng/kg/min) were studied on mean arterial pressure (MAP), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), filtration fraction (FF), total renal vascular resistance (TRVR), and urinary albumin excretion rate (UAER) in 11 IDDM and 11 NIDDM microalbuminuric patients. Angiotensin II infusion changed MAP from 100 +/- 3 mmHg at baseline to 105 +/- 3, 111 +/- 3, and 116 +/- 3 mmHg (P < 0.001), ERPF from 542 +/- 29 to 478 +/- 24, 429 +/- 23, and 382 +/- 19 ml/min (P < 0.001), FF from 20.2 +/- 0.06 to 23.1 +/- 0.7, 27.1 +/- 1.1, and 29.8 +/- 1.2% (P < 0.001), and TRVR from 9454 +/- 809 to 11,158 +/- 930, 13,310 +/- 1206, and 15,538 +/- 1362 dyne s cm-5 (P < 0.001). GFR and UAER, however, did not change significantly. Therefore, during angiotensin II infusion ERPF decreased, while FF and TRVR increased. As UAER and GFR remained unchanged, the presumed rise in intraglomerular capillary pressure by exogenous angiotensin II did not increase UAER. We suggest that during manipulation of the renin-angiotensin system, as in other renal diseases with proteinuria, factors other than glomerular transcapillary hydraulic pressure determine the degree of urinary albumin loss in microalbuminuric IDDM and NIDDM patients.
 ...
PMID:Urinary albumin excretion rate during angiotensin II infusion in microalbuminuric patients with insulin and non-insulin-dependent diabetes mellitus. 913 45

To investigate whether augmented calcium influx is involved in the mechanism of the enhanced proliferation of vascular smooth muscle cells (VSMCs) in diabetes, we studied the association between proliferation and cytosolic free calcium concentration ([Ca2+]i) in cultured aortic VSMCs from spontaneously diabetic Goto-Kakizaki (GK) and Wistar rats. Serum, angiotensin II and Bay K 8644, a voltage-dependent Ca2+ channel (VDC) agonist, stimulated the proliferation of VSMCs; the magnitude was greater in VSMCs from GK than Wistar rats. VDC blockers, verapamil and nicardipine, inhibited Bay K 8644-induced cell proliferation, and the difference in the proliferation of VSMCs between GK and Wistar rats disappeared. Angiotensin II-induced proliferation was only partially inhibited by VDC blockers, and enhanced proliferation of GK-VSMCs was still observed. Bay K 8644 and angiotensin II increased [Ca2+]i, and the increase was augmented in GK-VSMCs. Bay K 8644-induced [Ca2+]i increase was completely inhibited by pretreatment with verapamil or removal of extracellular Ca2+, suggesting that VDC is associated with this increase. Although angiotensin II-induced [Ca2+]i increase was not affected by verapamil, removal of extracellular Ca2+ slightly but significantly attenuated angiotensin II-induced [Ca2+]i increase, suggesting that VDC blocker-insensitive receptor-activated Ca2+ influx is involved. These results indicate that augmented Ca2+ influx via VDC and a receptor-activated pathway may be involved in the mechanism of the enhanced proliferation of VSMCs from GK rats.
 ...
PMID:Augmented Ca2+ influx is involved in the mechanism of enhanced proliferation of cultured vascular smooth muscle cells from spontaneously diabetic Goto-Kakizaki rats. 919 69

Both the density and level of mRNA encoding insulin receptors in the kidney are inversely related to the dietary sodium content, suggesting a feedback mechanism that limits the insulin-induced sodium retention when extracellular fluid volume is expanded. Because angiotensin II affects tissue sensitivity to insulin in humans, we investigated whether angiotensin II affects insulin receptor binding and mRNA levels in the kidney, liver, and renal arteries of normal rats and rats with streptozotocin-induced diabetes mellitus. Non-diabetic and diabetic rats were infused for 7 days with either vehicle or angiotensin II at a rate of 200 ng. kg-1. min-1. In a separate experiment, normal rats were treated with an angiotensin converting enzyme inhibitor (captopril, 100 mg/dl in the drinking water) or vehicle for 7 days. Regional analysis of insulin receptor binding in the kidney and renal arteries was performed by an in situ technique using computerized microdensitometry and emulsion autoradiography. Insulin receptor mRNA levels were determined in renal and hepatic tissue by Northern blot hybridization and normalized with 28S rRNA. No differences in blood pressure were observed among diabetic and non-diabetic rats infused with either vehicle or angiotensin II, whereas captopril-treated rats had significantly lower blood pressure levels than their respective controls. Angiotensin II significantly decreased plasma renin concentration in both non-diabetic and diabetic rats. Insulin receptor number was significantly greater in the renal cortex of diabetic rats than in non-diabetics, whereas no significant differences were found in the outer medulla, inner medulla, or renal arteries. Angiotensin II infusion did not affect either the number or affinity of insulin receptors in any of the renal regions studied. Insulin receptor mRNA levels were significantly greater in the kidney and liver of diabetic rats than in non-diabetics and were not affected by angiotensin II infusion. Similar to angiotensin II infusion, captopril treatment did not affect either renal insulin receptor binding or mRNA levels. Thus, diabetic rats have increased insulin receptor binding and mRNA levels in comparison to non-diabetic rats. Angiotensin II infusion and captopril treatment do not affect insulin receptor binding and mRNA levels in the kidney, arguing against a role for this peptide in the modulation of renal sensitivity to insulin.
 ...
PMID:Effects of angiotensin II on insulin receptor binding and mRNA levels in normal and diabetic rats. 966 61

Dietary sodium restriction has a variety of effects on metabolism, including activation of the renin-angiotensin system. Angiotensin II has complex metabolic and cardiovascular effects, and these may be relevant to the effects of both nonpharmacological and pharmacological interventions in noninsulin-dependent diabetes mellitus (NIDDM). We have assessed the effect of dietary sodium restriction on insulin sensitivity and endogenous glucose production in eight normotensive patients with diet-controlled NIDDM who underwent hyperinsulinemic clamp studies in a randomized, double-blind, placebo-controlled cross-over protocol after two 4-day periods on sodium replete (160 mmol/day) and sodium deplete (40 mmol/day) diets. Mean +/- SD 24-h urinary sodium was 197 +/- 76.0 mmol (replete) and 67 +/- 19.5 mmol (deplete), P = 0.03. Insulin sensitivity was 42.0 +/- 11.3 mumol/kg.min (replete) and 37.0 +/- 11.6 mumol/kg.min (deplete), P = 0.04 (a reduction of 12%). Blood pressure was 130 +/- 21/78 +/- 11 mmHg (replete) and 128 +/- 12/73 +/- 10 mmHg (deplete). Dietary sodium restriction may result in a decrease in peripheral insulin sensitivity in normotensive patients with NIDDM, possibly via an elevation in prevailing angiotensin II concentrations.
 ...
PMID:Dietary sodium restriction impairs insulin sensitivity in noninsulin-dependent diabetes mellitus. 958 54

Angiotensin II (AII) acts by 2 types of receptors: the ATI receptor which mediates its actions on vasoconstriction, renin (inhibition) and aldosterone (stimulation) secretions, cellular proliferation and angiogenesis and the non-AT1 (often called AT2) receptors. Mainly expressed in the embryon these latter may favor cellular differentiation and recruitment of collateral circulation. Angiotensin converting enzyme inhibitors (ACEI) decrease the synthesis of All and therefore the stimulation of both receptor types whereas AT1-receptor antagonists (AT1RA) block only the stimulation of these latter and increase the stimulation of AT2 receptor since they increase the production of All secondarily to the inhibition of the feedback of renin secretion by All. Experimentally ACEI and AT1RA decrease angiogenesis and cellular proliferation and favor cellular differentiation which could explain the protective effect of ACEI against cancer suggested recently in a Scotish study. Despite of their common suppressive effect on angiogenesis AT1RA may better than ACEI protect against ischemic events specially the cerebral ones because they favor the rapid recruitment of collateral circulation. This has been demonstrated for losartan in case of abrupt ligation of the carotid in the gerbil since its previous administration protects against fatal cerebral ischemia whereas its previous administration with enalapril abolishes this protection. These data may explain why, in the CAPP trial, captopril which has prevented more effectively diabetes occurrence could not be proved superior to diuretics and/or betablocker in the prevention of myocardial infarction and specially of strokes for which exist on the contrary a suspicion of a lower protection. Therefore a comparative trial between AT1RA and ACEI in the prevention of stroke recurrence should appear as a priority for Public Health and Pharmaceutical Industry Authorities.
 ...
PMID:[Duality of angiotensin II receptors and risk for stroke and cancer: what is the connection?]. 1036 Jan 91

We evaluated the effects of angiotensin II and an angiotensin-converting enzyme inhibitor (cilazapril) on nerve blood flow (NBF) and electrophysiology in control and diabetic rats. When applied locally to the sciatic nerve, the dose-response curve of angiotensin II was more potent in experimental diabetic neuropathy (EDN) than control rats. No difference existed in plasma angiotensin II levels between EDN and controls. The rats were given typical rat pellets or pellets treated with 10 mg/kg per day cilazapril for 4 weeks. Diabetes caused a significant reduction in NBF, nerve conduction velocity, and compound muscle action potential (CMAP) amplitudes. NBF was significantly increased in diabetic rats supplemented with cilazapril diet, and nerve conduction velocity and amplitudes of the CMAP were also improved after 4 weeks on this diet. Direct application 10(-3) mol/L cilazapril on sciatic nerve did not increase NBF in normal and EDN rats. We topically applied the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine, on sciatic nerve and observed reduced inhibition of NBF in EDN, which was correctable with a cilazapril diet. These results suggest that diabetic neuropathy may have an increasing vasopressor action with angiotensin II and this is likely to be the mechanism of NOS inhibition. Angiotensin II-converting enzyme inhibitors may have potential in the treatment of diabetic neuropathy.
 ...
PMID:Altered vasoreactivity to angiotensin II in experimental diabetic neuropathy: role of nitric oxide. 1039 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>