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)

ODU Plaque-susceptible rats (ODUS/Odu) exhibit markedly heavy plaque formation in the lower incisors and develop both periodontal pockets and gingivitis after being fed a commercially available powder diet. These rats have been established as an inbred strain. We have demonstrated that the ODUS/Odu are a very suitable experimental model for studying periodontitis. We already reported about the allelic distribution, changes of plaque formation and body weight, biochemical nature, toxic activity, vascular permeability factor and bradykinin inactivating factor of the plaque, histological and immunological studies, the pH in the periodontal pocket, amount of saliva, IgA in the saliva, salivary kallikrein, the relationship between sialic acid in the saliva and the serum, leukocyte functions (chemotaxis and superoxide anion) in ODUS/Odu, histamine, mast cell, free radicals, superoxide dismutase activities in gingiva and gingival nerve fibers with substance P or calcitonin gene-related peptide, and effect of diabetes. Streptozotocin-induced diabetic ODUS/Odu may be a useful tool for studying the pathological mechanisms in the development of periodontal tissue breakdown in diabetes. ODUS/Odu should help to further establish the utility of this strain as a model for experimental periodontal disease.
 ...
PMID:[Experimental periodontitis in rats]. 762 82

Angiotensin II (Ang II) has been implicated in the pathogenesis of the vascular injury associated with hypertension and diabetes mellitus. Increased vascular permeability is an important early manifestation of endothelial dysfunction and the pathogenesis of atherosclerosis. How Ang II contributes to endothelial dysfunction and promotes an increase in vascular permeability is unknown but is classically attributed to its pressor actions. We demonstrate that human vascular smooth muscle cells express abundant mRNA for vascular permeability/endothelial growth factor. Vascular permeability factor is a 34- to 42-kD glycoprotein that markedly increases vascular endothelial permeability and is a potent endothelial mitogen. Ang II potently induced a concentration-dependent (maximal, 10(-7) mol/L) and time-dependent increase in vascular permeability factor mRNA expression by human vascular smooth muscle cells that was maximal after 3 hours and diminished by 24 hours. Ang II-induced vascular permeability factor mRNA expression by human vascular smooth muscle cells was inhibited by the specific Ang II receptor antagonist losartan (DuP 753), confirming that this is an Ang II receptor subtype 1-mediated event. These results describe a new action of Ang II on human vascular smooth muscle, notably the induction of vascular permeability factor mRNA expression. The wide spectrum and potent activity of vascular permeability factor suggest a novel mechanism whereby Ang II could locally and directly influence the permeability, growth, and function of the vascular endothelium independent of changes in hemodynamics.
 ...
PMID:Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells. 773 26

In the retinas of streptozotocin-induced diabetic rats, the relationship between the expression of vascular endothelial growth factor (VEGF) and the breakdown of the blood-retinal barrier (BRB) was investigated. VEGF mRNA expression was examined by in situ hybridization and VEGF protein expression was examined by immunohistochemistry. BRB breakdown was immunohistochemically demonstrated by detecting extravasation of albumin. In diabetic retinas, VEGF mRNA was expressed by the following cells: (a) ganglion cells, (b) glial cells such as astrocytes and Muller cells, whose cell processes are closely associated with retinal vessels, (c) smooth muscle cells and pericytes in the vessel walls, and (d) the retinal pigment epithelium. In diabetic retinas, BRB breakdown was immunohistochemically detected, and VEGF protein expression was markedly increased in comparison to that in the control retinas. The rates of both BRB breakdown and VEGF immunoreactivity increased in proportion to the duration of diabetes. In addition, the rate of BRB breakdown was much higher in vessels with VEGF immunoreactivity than in vessels without VEGF immunoreactivity. These findings indicate that VEGF has a major promoting effect on BRB breakdown in simple diabetic retinopathy. VEGF immunoreactivity was distributed throughout all layers of the retinas, and were most prominently observed in the nerve fiber layer, especially near the optic disc and around large vessels. These two regions coincide with the sites wherein BRB breakdown is clinically detected by fluorescein angiography in diabetic patients. Neovascularization in proliferative diabetic retinopathy is also most commonly observed in these two regions. Because VEGF promotes endothelial proliferation, these findings suggest that VEGF plays a role in the budding of retinal neovascularization and, as a result, could induce proliferative diabetic retinopathy.
 ...
PMID:The relation between expression of vascular endothelial growth factor and breakdown of the blood-retinal barrier in diabetic rat retinas. 860 91

Endocrine organs, such as the pancreatic islets of Langerhans, contain permeable, fenestrated endothelium that allows direct access of endocrine cells to the blood stream. Factors that control differentiation and maintenance of this highly specialized endothelium remain unknown. Vascular endothelial growth factor (VEGF) is a multifunctional growth factor that may be responsible for the homeostasis of endocrine endothelium; it is a selective mitogen for endothelial cells and is able to permeabilize endothelium. We have analyzed the expression of VEGF mRNA and protein in pancreatic islet cells of normal mice and during the different stages of tumor progression in a transgenic mouse model of beta-cell carcinogenesis. The 120-amino acid and the 164-amino acid isoforms of VEGF are expressed in normal islets of Langerhans and are moderately up-regulated during the stages of tumor development. Two high-affinity receptors for VEGF, flt-1 and flk-1, are expressed by endothelial cells both in normal islets and in the stages of tumorigenesis; these receptors are not up-regulated during this process. Our data raise the possibility that VEGF is involved in the maintenance of permeable endothelium in islets of Langerhans, an observation that may have implications for islet cell physiology and diabetes. While VEGF may also play an important role in the growth of new blood vessels during islet cell tumorigenesis, it cannot be the only factor required for the activation of tumor angiogenesis.
 ...
PMID:Vascular endothelial growth factor and its receptors, flt-1 and flk-1, are expressed in normal pancreatic islets and throughout islet cell tumorigenesis. 861 12

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a potent enhancer of microvascular permeability and a selective endothelial cell growth factor. In normal human kidney, VPF/VEGF mRNA and protein are strongly expressed by visceral glomerular epithelial cells, and VPF/VEGF may be an important regulator of glomerular endothelial cell function. This study examined 47 renal biopsies from patients with a variety of glomerular diseases for expression of VPF/VEGF mRNA and protein by in situ hybridization and immunohisto-chemistry. In many glomerular diseases, VPF/VEGF-expressing cells were decreased in number or absent in areas of focal or global glomerular sclerosis. Decreased numbers of VPF/VEGF-expressing cells in glomeruli were also noted in amyloidosis, diabetes, crescentic glomerulonephritis, and diffuse endocapillary proliferative glomerulonephritis associated with systemic lupus erythematosus. Normally, release of VPF/ VEGF must be under strict control because it is some 50,000 times more potent than histamine as an inducer of microvascular permeability. Damage to visceral epithelial cells in a variety of glomerular diseases has the potential for releasing relatively large amounts of VPF/VEGF locally, leading to increased glomerular permeability. In addition, because VPF/ VEGF is also an endothelial growth factor, the loss of normal, controlled secretion of VPF/VEGF after damage to visceral epithelial cells could lead to important alterations in glomerular endothelial cell function.
 ...
PMID:Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases. 873 99

The introduction of ocular photocoagulation, almost thirty years ago, was the first successful prevention of blindness from diabetic retinopathy in some patients. The development of lasers, and the growing knowledge of indications for their application, reached the point at which the growth of new blood vessels could be stopped or reversed, and legal blindness from macular oedema avoided in about half of the treated eyes. The attempts at the very prevention of diabetic retinal microvascular complications at some more physiological, even molecular level, aside from the palliative treatment by photocogulation, brought some new and exciting results which are reviewed here. First, and foremost, is the understanding of the importance of the tight blood glucose control which, if started early and kept long enough, slows down the development of retinal lesions and offers a better prognosis for vision in a substantial number of diabetic patients. Second, the development of a unique animal model of proliferative retinopathy which mirrors human disease both chemically and histopathologically offers a field for investigation of both pathogenesis and therapy of this most dreadful complication of diabetes. Finally, there is a bulk of new evidences about the key role of vascular endothelial growth factor/vascular permeability factor in ocular angiogenesis which will probably result in the new approach to the prevention of neovascular growth by inhibition or modulation of VEGF/VPF activity.
 ...
PMID:[On the threshold of new treatment of diabetic retinopathy]. 922 17

Recent studies have suggested that advanced glycation end products (AGEs) are involved in the development of diabetic complications. To assess the pathogenic role of AGEs and vascular endothelial growth factor (VEGF) in the development of retinal neovascularization in diabetic retinopathy, we investigated the effect of AGEs on induction of VEGF by retinal Muller cells and measured AGE and VEGF concentrations in the vitreous of patients with proliferative diabetic retinopathy (PDR) and nondiabetic patients. The expression of VEGF mRNA and the production of VEGF protein by cultured Muller cells were enhanced by the presence of AGEs. The vitreous concentrations of AGEs and VEGF were both elevated in patients with PDR compared with patients without diabetes (P < 0.01). There was a moderate positive correlation between the levels of crossline and VEGF (r=0.698, P < 0.01). Elevation of AGEs in the vitreous may promote intraocular neovascularization in diabetic retinopathy through production of VEGF from Muller cells.
 ...
PMID:Advanced glycation end products induce expression of vascular endothelial growth factor by retinal Muller cells. 924 19

Hyperglycemia is an independent risk factor for the development of diabetic microvascular disease. Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a potent cytokine family that induces angiogenesis and markedly increases endothelial permeability. VPF is produced by many cell types, including vascular smooth muscle (VSM) cells, and has been implicated in the pathogenesis of neovascularization and endothelial dysfunction in diabetes. This study used cultured human VSM cells to study the regulation of VPF production and determine whether elevated glucose concentrations, per se, are a sufficient stimulus for increased VPF production by human cells. In human VSM cells, high extracellular glucose concentrations (20 mmol/l) increased VPF mRNA expression within 3 h (3-fold vs. glucose 5 mmol/l) and significantly increased VPF peptide production within 24 h (1.5-fold) in a time- and glucose concentration-dependent manner. The high glucose-induced increase in VPF mRNA expression was rapidly reversed after normalizing the extracellular glucose concentration and was specific for a high D-glucose concentration, as these effects were not reproduced by osmotic control media containing elevated concentrations of mannitol or L-glucose. High glucose concentrations activate protein kinase C (PKC) in human VSM cells, and PKC inhibitors (H-7 or chelerythrine chloride) or PKC downregulation each prevented the glucose-induced increases in VPF mRNA expression by human VSM cells. In conclusion, high glucose concentrations directly increase VPF mRNA expression and peptide production by human VSM cells via a PKC-dependent mechanism. These results demonstrate a cellular mechanism, whereby hyperglycemia could directly contribute to the development of endothelial dysfunction and neovascularization in diabetes.
Diabetes 1997 Sep
PMID:Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro. 928 52

Insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF) levels are correlated with retinal ischemia-associated intraocular neovascularization in humans. Since VEGF is required for iris and retinal neovascularization in animal models of retinal ischemia, we tested whether IGF-I could act as an indirect angiogenic factor by increasing VEGF gene expression. IGF-I increased retinal pigment epithelial (RPE) cell VEGF mRNA in a concentration-dependent manner with an EC50 of 7 nmol/1 (53.6 ng/ml). RPE and bovine smooth muscle cells exposed to 50 nmol/l (383 ng/m1) IGF-I achieved peak VEGF mRNA expression within 2 h. IGF-I-treated RPE cells increased VEGF protein levels in conditioned media and stimulated capillary endothelial cell proliferation. Blockade of the IGF-I receptor with a neutralizing antibody abrogated the VEGF increases in RPE cells. Further, hypoxia-mediated and IGF-I-mediated increases in VEGF mRNA and protein levels were additive in RPE cells, and the hypoxia-induced VEGF increases were independent of endogenous IGF-I. VEGF promoter activity was enhanced by IGF-I in RPE cells, but VEGF transcript half-life was unaltered. In summary, the supplementation of RPE and smooth muscle cell cultures with IGF-I at 5-100 nmol/l increased VEGF mRNA and secreted protein levels. The VEGF increases in RPE cells occurred primarily through enhanced transcription of the VEGF gene and via the IGF-I receptor. Elevated IGF-I levels may promote neovascularization through increased retinal VEGF gene expression.
Diabetes 1997 Oct
PMID:Regulation of vascular endothelial growth factor expression by insulin-like growth factor I. 931 59

Vascular endothelial growth factor (VEGF), in addition oto its growth-promoting effects on endothelial cells, can also increase vascular permeability and monocyte migration. It has therefore been implicated in the pathogenic neovascularization associated with diabetic retinopathy and atherosclerosis. However, the factors regulating VEGF expression in the vascular wall are not fully understood. In this study, we examined the regulation of VEGF expression in vascular smooth muscle cells (VSMC) by hyperglycemia as well as by angiotensin II (ANG II). We also examined whether the 12-lipoxygenase (12-LO) product 12-hydroxyeicosatetraenoic acid (12-HETE) can alter VEGF expression, since 12-LO products of arachidonic acid have angiogenic properties, and ANG II as well as high glucose (HG, 25 mM) can increase 12-LO activity and expression in VSMC. Studies were carried out in human (HSMC) or porcine VSMC (PSMC), which were cultured for at least two passages under normal glucose (NG, 5.5 mM) or HG conditions. HG culture alone increased the expression of VEGF mRNA and protein in both HSMC and PSMC. Furthermore, ANG II treatment significantly induced VEGF mRNA and protein expression only in VSMC cultured in HG and not NG. In addition, 12-HETE significantly increased VEGF mRNA and protein expression in HSMC cultured in NG as well as in HG. Cells cultured in HG also secreted significantly greater amounts of VEGF into the culture medium. These results suggest that elevated VEGF production under HG conditions may play a role in the accelerated vascular disease observed in diabetes.
 ...
PMID:Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells. 937 57


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