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)

Diabetic patients are at a 10- to 20-fold increased risk for the development of critical limb ischemia. Vascular endothelial growth factor (VEGF) is critical for the development of collateral blood vessels, which can effectively bypass peripheral arterial occlusions. We therefore set out to determine if the regulation of VEGF in patients with peripheral vascular disease differs in diabetic and nondiabetic patients. Diabetic and nondiabetic patients with peripheral vascular disease were divided into those with or without critical limb ischemia as defined by clinical criteria (rest pain, nonhealing ulcer). Monocytes from peripheral blood were isolated from all patients and the hypoxic induction of VEGF was determined in vitro. In patients without diabetes, we found that there was no significant difference in the hypoxic induction of VEGF between patients with or without critical limb ischemia. However, in diabetic patients we found that patients with critical limb ischemia produced significantly more VEGF than patients without critical limb ischemia (6.3 +/- 1.3 vs. 2.1 +/- 0.3, p < 0.015). We conclude that diabetic patients with critical limb ischemia do not have an impairment in the ability to produce VEGF with hypoxia. Contrary to current dogma, treatment paradigms directed at increasing VEGF production in the diabetic patient with critical limb ischemia might not be beneficial.
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PMID:Regulation of VEGF in diabetic patients with critical limb ischemia. 1141 92

This study was designed to evaluate whether vascular endothelial growth factor serum concentrations may identify adolescents with onset of type 1 diabetes during childhood at greater risk to develop persistent microalbuminuria and incipient diabetic nephropathy. In January 1989, vascular endothelial growth factor serum levels were measured in 101 normoalbuminuric diabetic children and adolescents (aged 7-14.9 yr; onset of diabetes before age 18 yr; duration of diabetes >7 yr). Participants were clinically examined at baseline and annually thereafter. Vascular endothelial growth factor serum concentrations were measured every year during the 8-yr follow-up period. Over 8 yr, 11 of 101 patients (10.9%) developed persistent microalbuminuria; no patient developed overt nephropathy. The risk of developing microalbuminuria was higher in children with increased vascular endothelial growth factor serum levels (using 160 pg/ml as the arbitrary cut-off point; group 1) compared with those with normal vascular endothelial growth factor serum levels at the beginning of the study (group 2; 19.2 vs. 2.0%; P < 0.01; sensitivity, 90.9%; specificity, 53.3%). The odds ratio for the occurrence of microalbuminuria after adjustment for confounding variables (albumin excretion rate, sex, hemoglobin A(1c), mean blood pressure, cholesterol, and triglycerides) in type 1 diabetic adolescents with elevated vascular endothelial growth factor serum levels was 4.1 (95% confidence interval, 2.0-10.9). These results suggest that vascular endothelial growth factor serum concentrations may be one of the predictors and risk factors for microalbuminuria and incipient diabetic nephropathy in adolescents and young adults with onset of diabetes during childhood. Persistently increased vascular endothelial growth factor serum levels may help to identify normotensive, normoalbuminuric patients with type 1 diabetes who are predisposed to develop persistent microalbuminuria later in life.
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PMID:Increased vascular endothelial growth factor serum concentrations may help to identify patients with onset of type 1 diabetes during childhood at risk for developing persistent microalbuminuria. 1150 26

Cilostazol is a new phosphodiesterase inhibitor with anti-platelet and vasodilatory properties. Cilostazol and pentoxifylline are the only two drugs that have been approved for the treatment of patients with intermittent claudication. However, the mechanisms by which exercise tolerance is improved remain unclear. Vascular endothelial growth factor (VEGF) is a potent endothelial mitogen that results in angiogenesis when overexpressed in human subjects. To assess the potential role of VEGF in the improvement in exercise tolerance, we investigated plasma levels of VEGF in 50 patients with intermittent claudication who were allocated randomly to groups receiving cilostazol (n=17), pentoxifylline (n=17) or placebo (n=16). Patients given either cilostazol or pentoxifylline showed a significant improvements in maximal walking distance compared with the placebo group (34 m and 33 m respectively, compared with 5 m; both P<0.05). Neither cilostazol nor pentoxifylline increased the ankle-brachial index after treatment. Circulating VEGF levels were increased (from 116+/-29 to 169+/-45 pg/ml; P=0.002), and the levels of VEGF were correlated significantly with exercise tolerance in a positive direction (r=0.88, P=0.004), in those patients treated with cilostazol that did not have diabetes mellitus. In contrast, VEGF levels remained stable after the administration of pentoxifylline. These findings suggest that VEGF may contribute to the cilostazol-related improvement in exercise tolerance in non-diabetic patients. However, pentoxifylline did not affect VEGF levels, although a similar improvement in maximal walking distance was achieved. Thus the mechanisms involved in the pentoxifylline-treated group were different from those in the cilostazol-treated group, and require further study.
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PMID:Differential effects of cilostazol and pentoxifylline on vascular endothelial growth factor in patients with intermittent claudication. 1152 48

Vascular endothelial growth factor (VEGF) and insulin-like growth factor-I (IGF-I) both play a pivotal role in diabetic microangiopathy. This study assessed the relationship between capillary permeability as a marker of endothelial dysfunction and serum VEGF and IGF-I levels in normotensive diabetics. Subjects were 10 Type 1 (6/4, male/female, age: 30 [mean] +/- 5 [SD] years, HbA1c: 7.5 +/- 1.1 %), 13 Type 2 diabetics (9/4, m/f; 63 +/- 7 years, 8.3 +/- 1.8 %), and 24 age- and sex-matched control subjects. We determined nailfold capillary permeability by intravital fluorescence videomicroscopy after intravenous injection of sodium-fluorescein. Serum VEGF, free and total IGF-I, IGF binding protein (IGFBP)-1, IGFBP-3, and insulin levels were measured by specific immunoassays. Capillary permeability was increased in both types of diabetes patients compared to age- and sex-matched controls. In Type 1 diabetics, fluorescence light intensities increased over time, reaching significance 30 minutes after dye injection. Type 2 diabetics already revealed an early onset of elevated fluorescence light intensities after one minute. Capillary permeability showed a significant positive correlation with VEGF levels in Type 1 diabetics, (r = 0.76, p < 0.05; 20 min after dye injection) but with free IGF-I levels in type 2 diabetics (r = 0.65, p < 0.05; 5 min after dye injection). IGFBP-3 correlated negatively with capillary permeability in both diabetes types, whereas IGFBP-1 levels correlated positively in Type 2 patients. In conclusion, capillary permeability is increased in both types of diabetes mellitus. However, VEGF and IGF-I may differentially affect microvascular permeability depending on the diabetes type.
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PMID:Microvascular permeability is increased in both types of diabetes and correlates differentially with serum levels of insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF). 1175 56

Vascular endothelial growth factor (VEGF), a major mediator of vascular permeability and angiogenesis, may play a pivotal role in mediating the development and progression of diabetic retinopathy. In the present study, we examined the genetic variations of the VEGF gene to assess its possible relation to diabetic retinopathy in type 2 diabetic patients. Among seven common polymorphisms in the promoter region, 5'-untranslated region (UTR) and 3'UTR of the VEGF gene, genotype distribution of the C(-634)G polymorphism differed significantly (P = 0.011) between patients with (n = 150) and without (n = 118) retinopathy, and the C allele was significantly increased in patients with retinopathy compared with those without retinopathy (P = 0.0037). The odds ratio (OR) for the CC genotype of C(-634)G to the GG genotype was 3.20 (95% CI 1.45-7.05, P = 0.0046). The -634C allele was significantly increased in patients with nonproliferative diabetic retinopathy (non-PDR) (P = 0.0026) and was insignificantly increased in patients with proliferative diabetic retinopathy (PDR) (P = 0.081) compared with patients without retinopathy, although frequencies of the allele did not differ significantly between the non-PDR and PDR groups. Logistic regression analysis revealed that the C(-634)G polymorphism was strongly associated with an increased risk of retinopathy (P = 0.0018). Furthermore, VEGF serum levels were significantly higher in healthy subjects with the CC genotype of the C(-634)G polymorphism than in those with the other genotypes. These data suggest that the C(-634)G polymorphism in the 5'UTR of the VEGF gene is a novel genetic risk factor for diabetic retinopathy.
Diabetes 2002 May
PMID:A common polymorphism in the 5'-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. 1197 67

Vascular endothelial growth factor (VEGF) is a potent stimulator of vascular proliferation and permeability. Ovarian granulosa cells have been identified as a major source of the cytokine and r-hCG was able to stimulate VEGF mRNA expression in vitro. In this study we have investigated the immediate effect of ovulation induction with hCG on peripheral VEGF levels in 6 women with primary infertility enrolled in the IVF/ET program. The patients underwent a 24-hour continuous blood withdrawal with sampling intervals of 15 minutes starting from 5 hours before ovulation induction with 10.000 IU hCG. Ovulation induction with hCG had no significant immediate effect on mean peripheral VEGF levels. However, VEGF plasma levels did exhibit significant episodic fluctuations with rapid increases every 90-120 minutes without any relation to circulating hCG levels. Taken together, the results of this study suggest that VEGF is released episodically and that systemic VEGF levels are not acutely altered by ovulation induction with hCG.
Exp Clin Endocrinol Diabetes 2002 May
PMID:VEGF plasma pattern in ovulation induction: evidence for an episodic secretion and lack of immediate effect of hCG. 1201 73

Angiogenesis, the formation of new blood vessels from existing vascular endothelium, is essential for tumor growth. Vascular endothelial growth factor (VEGF) is an endotheliumspecific mitogen and regulator of angiogenesis. Angiogenesis has been associated to the malignant phenotype of pheochromocytomas and is readily observed in experimental pheochromocytomas. Although VEGF gene expression has already been demonstrated in the rat PC12 cell line, the detailed mechanisms of action are not known. We have, therefore, studied angiogenesis in the rat PC12 pheochromocytoma cell line in vitro and in vivo. VEGF gene expression and accumulation of VEGF protein in cytoplasm and conditioned medium of PC12 cells was found. Conditioned medium from PC12 cells significantly increased proliferation of VEGF-dependent endothelial cells from human umbilical veins, and this effect reversed upon addition of a neutralizing anti-VEGF antibody. Dexamethasone and nerve growth factor (NGF) increased VEGF mRNA expression and accumulation of VEGF protein of PC12 subclones with established metastatic activity in vivo. PC12 cells xenotransplanted to nude mice had marked VEGF expression and induced host angiogenesis, confirmed by the presence of CD34-positive endothelial cells in the experimental PC12 tumors. When NGF-primed PC12 cells were immobilized in Matrigel supplemented with rising concentrations of the growth factor and xenotransplanted, increasing NGF resulted in tumors with smaller areas of necrosis and increased vital tumor volume. These results suggest that VEGF is a mediator of angiogenesis in the PC12 pheochromocytoma cell line, and that dexamethasone and NGF affect VEGF expression. Our data further suggest that NGF may contribute to angiogenesis in experimental pheochromocytoma.
Exp Clin Endocrinol Diabetes 2002 Nov
PMID:In vitro and in vivo angiogenesis in PC12 pheochromocytoma cells is mediated by vascular endothelial growth factor. 1251 48

Vascular endothelial growth factor (VEGF) and its specific receptors FLT-1 and FLK-1 represent an important ligand-receptor system involved in angiogenesis and permeability. These factors are supposed to be influenced by ovarian steroids involved in developmental changes in female reproductive tissue as oviduct and uterus. The aims of this study were to assess the expression of VEGF and its receptor mRNAs during the early implantation period in porcine endometrium using real-time RT-PCR. Furthermore, effects of estradiolbenzoate (EB) and progesterone (P) on endometrium of ovariectomized (ovx) pigs were examined by RT-PCR and immunohistochemistry. A complete VEGF system was found in endometrial tissue using RT-PCR detecting the main VEGF isoform 188 aa, FLT-1 and FLK-1. A significant upregulation of the mRNAs of VEGF and its receptors was observed in the endometrium during the peri-implantation when compared with the pre-implantation period. Regarding endometrium of non-pregnant ovx-pigs an application of P led to elevated transcript levels of VEGF whereas mRNA-expression was reduced after EB treatment compared to non-treated ovx-animals. When pigs were administrated EB and P simultanously, a decrease in VEGF mRNA concentration was recorded. For FLT-1, none of the steroids increased mRNA expression compared to the ovx-group. Analysis of FLK-1 receptor mRNA demonstrated that only after EB + P treatment mRNA-expression was stimulated but stayed unchanged after P and EB when compared with the ovx-group. Immunohistochemistry revealed FLK-1 and VEGF proteins in glandular and luminal epithelia of the endometrium with emphasized staining after P and P + EB treatment of ovx-pigs. Summarized, altered VEGF and FLK-1 expression during the implantation period as well as under steroid hormones suggest this growth factor as a potent regulator of hyperpermeability supporting the angiogenic process in porcine endometrium.
Exp Clin Endocrinol Diabetes 2003 Feb
PMID:Regulation of the VEGF-system in the endometrium during steroid-replacement and early pregnancy of pigs. 1260 48

Vascular endothelial growth factor (VEGF) has been shown to play a major role in intraocular neovascularisation in ischaemic retinal diseases. The aim of this study was to evaluate the concentration of VEGF in vitreous, aqueous and epiretinal membranes of diabetic and non-diabetic patients, with other pathological conditions requiring surgical intervention. Higher VEGF concentration were found in samples from the eyes of diabetic patients versus other pathologies as well as in epiretinal membranes versus the other eye compartments in diabetic patients. However, high VEGF levels were also found in retinal detachment and proliferative vitreoretinopathy of non-diabetic patients. We concluded that VEGF is produced locally and plays a fundamental, but not specific, role in diabetic retinal neovascularisation and proliferation.
Exp Clin Endocrinol Diabetes 2003 Jun
PMID:Diabetic patients and retinal proliferation: an evaluation of the role of vascular endothelial growth factor (VEGF). 1284 59

Vascular endothelial growth factor (VEGF) is a glycoprotein that plays an important role in neovascularization and increases vascular permeability. We reported that VEGF is involved in motion pain of patients with rotator cuff disease by causing synovial proliferation in the subacromial bursa (SAB). The present study investigates whether VEGF is also involved in the development of shoulder contracture in diabetics with rotator cuff disease. We examined 67 patients with rotator cuff disease, including 36 with complete cuff tears, 20 with incomplete tears, and 11 without apparent tears (subacromial bursitis). The patients were into groups according to the presence or absence of diabetes (14 type II diabetics and 53 non-diabetics). Specimens of the synovium of the SAB were obtained from all patients during surgery. Expression of the VEGF gene in the synovium of the subacromial bursa was evaluated by using the reverse transcriptase polymerase chain reaction. The VEGF protein was localized by immunohistochemistry, and the number of vessels was evaluated based on CD34 immunoreactivity. The results showed that VEGF mRNA was expressed in significantly more diabetics (100%, 14/14) than in non-diabetics (70%, 37/53) (P=0.0159, Fisher's test). Investigation of VEGF isoform expression revealed VEGF121 in all 14 diabetics and in 37 of the 53 non-diabetics, VEGF165 in 12 of the 14 diabetics and in 21 of the 53 non-diabetics, and VEGF189 in 1 of the 14 diabetics and in 2 of the 53 non-diabetics. No VEGF206 was expressed in either group. VEGF protein was localized in both vascular endothelial cells and synovial lining cells. The mean number of VEGF-positive vessels and the vessel area were also significantly greater in the diabetics (p<0.015, Mann-Whitney U test). Synovial proliferation and shoulder joint contracture were more common in the diabetics (P=0.0329 and P=0.073, respectively; Fisher's test). The mean preoperative range of shoulder motion significantly differed in terms of elevation between two groups: 103.8 degrees in diabetics and 124.9 degrees in no diabetics (p=0.0039 Mann-Whitney U test). In contrast, external rotation did not significantly differ: 44 degrees in diabetics and 49 degrees in non-diabetics (p=0.4957, Mann-Whitney U test). These results suggest that VEGF121 and VEGF165 expression in the SAB is responsible for the development of shoulder joint contracture, especially in elevation, among type II diabetic patients with rotator cuff disease.
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PMID:Vascular endothelial growth factor 121 and 165 in the subacromial bursa are involved in shoulder joint contracture in type II diabetics with rotator cuff disease. 1455 30


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