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)

AGEs are nonenzymatically glycosylated adducts of proteins that accumulate in vascular tissues with aging and at an accelerated rate in people with diabetes; AGEs are closely linked to tissue damage due to their high reactivity in protein cross-linking. A macrophage-monocyte receptor system for AGE moieties is shown to mediate the uptake of AGE-modified proteins by a process that also induces cachectin-TNF, IL-1, IGF-I, and PDGF secretion. Thus, in addition to removing senescent glucose-modified proteins and cells, AGE-mediated release of growth-promoting factors may represent a mechanism by which macrophages signal mesenchymal cells the need for replacement of senescent proteins. The age of the macrophage correlates inversely with the binding and removal capacity of the AGE receptor, possibly preventing the clearance of cross-linked proteins and the compounding aging-related tissue damage. In addition to monocyte and macrophages, other cells express similar receptors for AGE-proteins, including endothelial cells, fibroblasts, and mesangial cells. Endothelial cell AGE-receptors mediate transcytosis of AGEs to the subendothelium, induce increased permeability, and enhance endothelium-dependent procoagulant activity. Renal mesangial AGE receptors mediate PDGF-dependent extracellular matrix protein production. Fibroblast AGE receptors may influence cellular proliferation by EGF and EGF-receptor regulation. These findings, in connection with the known abundance of AGEs in aged and diabetic tissues, indicate that AGE-ligand-receptor interactions are crucial for the development of age- and diabetes-related vascular tissue and renal pathology.
Diabetes 1992 Oct
PMID:Receptor-mediated interactions of advanced glycosylation end products with cellular components within diabetic tissues. 132 53

Neovascularisation is the biological process of forming new blood vessels. Many conditions can initiate neovascularisation including trauma or chronic ischaemia produced by diseases such as diabetes. Neovascularisation proceeds through a series of steps beginning with destruction of the basement membrane surrounding the microvascular endothelial cells, which allows endothelial cells to extend cytoplasmic buds in the direction of chemotactic factors. Migrating endothelial cells elongate, divide and eventually form tube structures which join to form mature new capillaries. Results of in vitro experiments, in vivo experiments, and clinical studies suggest that peptide growth factors can play key regulatory roles in each step of neovascularisation through both direct and indirect actions. At sites of vascular injuries, degranulating platelets release PDGF, IGF-I, EGF, and TGF-beta. Macrophages and neutrophiles drawn into the ischaemic or injured areas synthesise and release TGF-alpha, TGF-beta, and PDGF, and wounded endothelial cells secrete FGF. These peptide growth factors can stimulate migration, mitosis and differentiation of endothelial cells in culture and can induce neovascularisation in animal models. Clinical correlations suggest that peptide growth factors in the vitreous such as IGF-I and bFGF may promote diabetic retinopathy. As the biological mechanisms of neovascular growth factors become better understood, it may be possible to develop therapeutic approaches to selectively inhibit the peptide growth factors which regulate neovascular diseases.
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PMID:Neovascular growth factors. 171 36

The genetically diabetic db/db mouse is an excellent model to study the effect of diabetes on hormone receptors. The decrease of EGF binding sites could be detected in the hepatic microsomes of diabetic mice as early as 3 weeks of age. In addition, there was an age-related decrease in the autophosphorylating activity of EGF receptor isolated from the liver of diabetic mice. Estrone feeding (0.005%) partially restored this autophosphorylating activity. Northern blot analysis showed that the hepatic EGF receptor transcripts were dramatically decreased during the progression of diabetes and could be reversed by estrone feeding. Transfection experiments carried out on HepG2 cells using EGF receptor promoter (pERCAT-6) demonstrated that addition of 2 x 10(-8) M estrone stimulated chloramphenicol acetyltransferase activity. Our results suggest that estrone modulates EGF receptor by enhancing EGF receptor transcripts and the promoter activity of this gene.
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PMID:Estrone modulates the EGF receptor in the liver of db/db mouse. 175 81

Results obtained from our analyses of the role of hormones and growth factors in rat embryonic and fetal development are reviewed. Whole 10-day embryos or structures from 14-16-day fetuses (paws, intestines, reproductive tracts) were transplanted under the kidney capsule of syngeneic host rats of different age, sex, physiological state or level of nutrition. In intact hosts, fetal transplants grew almost as much as they would have if left in situ in the fetuses, and tissue differentiation in them was essentially normal. By contrast, growth of embryo transplants was severely depressed relative to their growth in utero, but tissue differentiation was only slightly retarded. Fetal paws grew equally well in female hosts widely diverging in age and growth rate. Thus, in such hosts growth of the fetal paw was highly independent of the growth rate of the hosts. In hosts in which growth was arrested or reduced by diabetes, hypophysectomy or food restriction, growth of paw transplants was impaired, but not as severely as that of the hosts themselves. Fetal skeletal structures were relatively independent of thyroid hormones (TH) for growth; TH dependence developed progressively postnatally. In pregnant hosts, fetal paw transplants grew as well during the first half of gestation as they did in virgin females. By contrast, during the second half of pregnancy and during both halves of the lactational period, growth of the transplants was significantly reduced. Host skeletal growth was also inhibited during late pregnancy and throughout lactation. The impaired growth during the second half of gestation was associated with a large reduction in serum IGF-I concentration and a resistance to the growth-promoting actions of GH. In the lactating hosts, serum IGF-I concentration returned almost to prepregnancy levels and the resistance to GH persisted, but at a reduced level. The direct effects of hormones, growth factors, and antibodies to them on growth and tissue differentiation in the transplants were assessed using infusion methods. Substances were infused into the renal artery of transplant-bearing kidneys via catheters attached to osmotic minipumps. The direct effects of insulin, GH, IGFs, basic FGF and EGF on transplant growth and tissue differentiation were evaluated. Insulin directly stimulated growth of transplants in diabetic hosts but GH did not have a direct effect in hypophysectomized rats. The growth-restorative effects of GH observed in hypophysectomized hosts were apparently mediated indirectly via IGF-I. Infused rat IGF-II (MSA) was more effective at stimulating growth of embryo transplants than was recombinant human IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Analysis of the role of hormones and growth factors in growth control and tissue differentiation using transplanted mammalian embryos and fetal structures. 184 45

Sixty thousand to 118,000 lower extremity amputations are performed each year in the United States. The combination of peripheral vascular disease and diabetes mellitus accounts for most cases, with diabetic patients representing 45% to 70% of all nontraumatic, lower extremity amputations. The 3-year survival rate after amputation is only 50%. As podiatric physicians, we are directly involved in limb preservation. Progress has occurred in both the diagnosis and treatment of lower extremity, chronic, nonhealing ulcers. An aggressive, comprehensive amputation intervention program is critical to those patients with refractory wounds to prevent the emotional, functional, and economic costs of limb loss. Recent developments in recombinant growth factors are making it possible to decrease the morbidity and mortality associated with defective angiogenesis, fibroblastic proliferation, collagen remodeling, and epithelial regeneration. Widespread use of growth factors will first occur in topical applications. Absorbable sutures, as well as impregnated bandages, are a likely method of delivering the growth factors to the wound site. Biotechnology companies are developing a stable formulation for bFGF topical application. Clinical trials have begun at various teaching hospitals across the United States for treatment of venous stasis ulcers. U.S. and European firms are collaborating to conduct the clinical studies required to obtain regulatory approvals leading to the sale of topical recombinant bFGF. Although U.S. approval is pending, European use of EFG in the healing of corneal incisions began several years ago. In the future, use of recombinant EGF topically with burn patients may permit earlier reharvesting of healed donor sites as well as coverage of larger graft areas. As some growth factors affect specific processes of healing and cell types, it may be necessary to combine growth factors for complex wounds. PDGF application in combination with other growth factors to incisional wounds may decrease postoperative complications with wound dehiscence while mediating inflammation and repair. In vivo experimental findings suggest that combinations of PDGF and insulin applied topically to wounds may increase the rate of wound repair in diabetics. It is also possible that even the normal healing process may be accelerated, thereby shortening postsurgical convalescence. Approval for internal administration of growth factors will require additional research and thorough clinical trials. The ability of TGF-beta to promote collagen formation may also relate to a metabolic condition such as osteoporosis, in which inadequate formation of collagen or other components of the bone matrix may contribute to pathogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Growth factor impact on wound healing. 193 39

We measured the amounts of epidermal growth factor receptor (EGFR) in plasma membranes from human placentas at term delivery in three groups: appropriate for gestational age (AGA), intrauterine growth-retarded (IUGR), and diabetes mellitus-complicated (DM) pregnancies. At the same time, EGFR mRNA levels were examined in three groups by dot and Northern blot analyses. Binding studies were performed using 125I-labeled human EGF as a ligand, and two classes (high and low) of binding sites were found in all specimens. Although dissociation constants (Kd) were not significantly different among three groups, the number of binding sites was significantly decreased in IUGR and DM placentas compared to that in the AGA group. Total cellular RNA was isolated from a part of the placentas used for binding studies using the guanidinium CsCl method, denatured, and dot blotted onto nitrocellulose filter. Poly(A)+ RNA was selected from the total RNA, electrophoresed in 1% agarose gel, and transferred onto nitrocellulose filters. Then, hybridization with 32P-labeled pE7 (a cDNA of EGFR), autoradiography, and densitometry were performed. The amounts of mRNA hybridized with pE7 were reduced in IUGR and DM placentas compared to that in the AGA group. The molecular sizes of EGFR mRNA were 10 and 5.6 kilobases in all three groups. These results suggest possible physiological actions of EGF on adequate feto-placental growth and development in human pregnancy.
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PMID:Decrease in epidermal growth factor receptor and its messenger ribonucleic acid levels in intrauterine growth-retarded and diabetes mellitus-complicated pregnancies. 202 55

Two IDD patients were stimulated with gonadotropins for IVF and ET. Both patients had high E2 response and greater than or equal to 5 preovulatory oocytes retrieved, normal fertilization and cleavage rates, and transfer; neither conceived. Follicular fluid showed levels of E2, P, A, hCG, and PRL similar to non-IDD. Epidermal growth factor could not be detected in FF. Insulin-dependent diabetes patients can undergo gonadotropin stimulation for IVF with customary responses. Their follicular milieu resembles that of non-IDD patients except for a lack of EGF.
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PMID:Gonadotropin stimulation for in vitro fertilization and embryo transfer in insulin-dependent diabetics: follicular response, oocyte quality, embryo development, and follicular environment. 210 62

Serum very low molecular weight growth factor like-activity (S-VLMGA, molecular weight less than 3,000) and serum and urinary epidermal growth factor (S-, U-EGF) were investigated in 180 patients of non-insulin-dependent diabetes mellitus (NIDDM) by bioassay using skin fibroblast cells (CCD-27 SK) and enzyme- and radio-immunoassay, respectively. S-VLMGA was slightly elevated in NIDDM patients with retinopathy (RET) and/or neuropathy (NEU), but slightly decreased in those with nephropathy (NEP) compared with patients without complications, though the differences were not significant (without complications: 122 +/- 9, with RET and/or NEU and without NEP: 145 +/- 15, all with NEP: 110 +/- 8% of increased growth activity, mean +/- SE). The similar tendencies were seen in S- and U-EGF in the same groups. However the changes in S-EGF were small and the decrease of U-EGF in patients with NEP was remarkable (U-EGF of without complications: 22.7 +/- 2.5, with RET and/or NEU and without NEP: 24.5 +/- 4.2, all with NEP: 17.6 +/- 3.2 ng/mg creatinine, mean +/- SE). Furthermore, S-VLMGA was inversely, but U-EGF was positively related with the creatinine urinary vs serum ratio. Thus the concentrations of VLMGA and EGF in serum and urine depend on a renal permeability.
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PMID:[Serum and urinary cell growth factors in non-insulin-dependent diabetes mellitus]. 223 55

Male rats (200 g) were rendered diabetic with one intraperitoneal injection of alloxan (150 mg/kg) or streptozotocin (60 mg/kg). In hyperglycemic animals within 3 hours after the injection, the binding of EGF to liver membranes decreased by 43-52%; the maximal drop was by 70% and persisted for the 20 days of the experiment. EGF receptors decreased in number with almost no changes in their affinity. Autophosphorylation of the receptors decreased parallel to the ligand binding. In animals that received lower doses and did not develop diabetes and in animals in whom diabetes was prevented by the injections of glucose (before alloxan) or nicotinamide (before streptozotocin) the binding of EGF to liver receptors remained normal. We conclude that the decreased expression of EGF receptors was caused by diabetes and not by the toxic effects of the diabetogenic compounds on the liver.
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PMID:Decreased expression of liver epidermal growth factor receptors in rats with alloxan and streptozotocin diabetes. 301 81

Emphasis is placed on the heterogeneity of the phenotypic presentation of PCOD. It is the common expression of an unknown number of disorders and thus is a sign and not a specific diagnosis. Two essential features are arrested follicular maturation and atresia of follicles. Normal folliculogenesis is described, emphasizing that a large number of areas could be subject to derangement causing PCOD. Any interference of the finely balanced sequence of events can lead to PCOD. The genetic defect causing familial PCOD is unknown and the initiating event remains undefined. Three families are described that illustrate four features of familial PCOD. A number of associated disorders such as diabetes, hyperinsulinemia, obesity, and hypertension are described. The potential importance of agents that modulate the LH and FSH activity that may cause PCOD is emphasized. The theoretic means by which similar male and female gonadal abnormalities may be coupled in families through growth factors EGF and alpha TGF are presented.
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PMID:Familial polycystic ovarian disease. 305 73


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