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)

Authors present one of the ocular diabetic complications--diabetic keratoepitheliopathy. The aim of this article is to summarize the knowledge about diabetic keratoepitheliopathy, its causes, manifestations and treatment options. Diabetes mellitus is associated with structural and functional disturbances in eyelids, conjunctiva and cornea. There are also changes in tear film present. Diabetic neuropathy resulting from the biochemical poor control of diabetes is the probable basic cause of the pathology. Mechanisms responsible for these changes are still not well understood. The corneal and conjunctival complications may occur spontaneously. But more often they arise from undue stress of intraocular surgery procedures. The incidence of diabetic keratoepitheliopathy in diabetic patients is high. However, it is rarely diagnosed. Effectiveness of symptomatic treatment with use of common medications is not satisfactory and it needs further investigation.
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PMID:[Diabetic complications within ocular surface]. 1734 49

We examined phenotypic changes during the wound healing process in the corneal epithelium of Goto-Kakizaki (GK) rats, a spontaneous model of type 2 diabetes mellitus. In this article, we provide an overview of our and other groups' research and describe the clinical features of diabetic keratopathy. We observed that the rate of corneal epithelial wound closure was decreased in GK rats compared with Wistar rats. Immunoreactivity for Cx43, K14, and Ki-67 was detected in the 2 layers of cells adjacent to the basement membrane in the corneal epithelium of GK rats, whereas only the single basal layer of cells was positive for these proteins in the corneal epithelium of Wistar rats. The frequency of Ki-67-positive cells was greater in GK rats than in Wistar rats in the intact corneal epithelium and during wound healing. The GK rat represents delayed corneal epithelial wound closure as well as that which is observed in human diabetic keratopathy. Furthermore, these results indicate a possibility of functional deviation in corneal epithelial cells with diabetes mellitus.
Cornea 2007 Oct
PMID:Deviated mechanism of wound healing in diabetic corneas. 1788 21

Proteins can interact with biological surfaces such as cell membrane, chaperones, cornea, bone, arteries, veins, and heart cavities of the cardiovascular system and also with non-biological surfaces including dialysis membranes and tubing, catheters, invasive surgical instruments, needles, and artificial implants. Fibrillation of amyloid proteins is implicated in many human diseases, including Alzheimer's, Parkinson's, and type II diabetes. Here, we show that heterogeneous surfaces accelerate the human insulin nucleation process that is the rate-determining step during amyloid fibril formation. The observed shorter lag (nucleation) phase correlates both with surface wettability and surface roughness. Surfaces promote faster nucleation possibly by increasing the local concentration of protein molecules. A composite parameter combining both surface wettability and roughness suggests that the ideal surface for slower nucleation should be hydrophilic and smooth. These findings provide a basis for designing suitable biomaterials and biomedical devices, especially those to resist amyloidosis.
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PMID:Surface-enhanced nucleation of insulin amyloid fibrillation. 1826 5

We examined changes in the ultrastructure and localization of major extracellular matrix components, including 5 types of collagen (type I, III, IV, VI, and VIII), laminin, fibronectin, and heparan sulfate proteoglycan in Descemet's membrane of the cornea of diabetic GK rats. In the cornea of diabetic GK rats, more long-spacing collagen fibrils were observed in Descemet's membrane than in the membrane of the nondiabetic Wistar rats. Both GK and Wistar rats showed an age-dependent increase in the density of the long-spacing collagen. Immunoelectron microscopy showed that type VIII collagen was localized in the internodal region of the long-spacing collagen, which was not labelled by any of the other antibodies used. The antidiabetic agents nateglinide and glibenclamide significantly suppressed the formation of the long-spacing collagen in the diabetic rats. Long-spacing collagen would thus be a useful indicator for studying diabetic changes in the cornea and the effect of antidiabetic agents.
Exp Diabetes Res 2008
PMID:Change in long-spacing collagen in Descemet's membrane of diabetic Goto-Kakizaki rats and its suppression by antidiabetic agents. 1877 68

Thyroidorbithopaty is inflammatory disease against the autoimmune reaction. Clinical symptoms are connected within-creasing the volume of retrobulbar tissues. As a result of the autoimmune reaction is reaching to the blow-up, thickening extrabulbar muscles, of appearance of the swelling of the inflammable body of the fat body and tear glands. Heightened retrobulbar pressure is leading to the exophthalmos of the eyeball. He can be a consequence of the exophthalmos insuffiency of eyelids, drying, ulcerations of the cornea. In external eyball muscles changes are leading to eyeball mobility limitation, the double vision, whereas the pressure on the optic nerve can be a reason of injuring it what next serious complications constitute thyroidorbitopathy. In the case active orbithopaty an immunosuppression is an essential way of curing. Disabled advanced form thyroidorbithopaty is a reading for curing applying treatment methods. Outside clinical symptoms among others findings of CT, MR examinations are deciding using it. A treatment is one of methods of operating intranasal curing, of endoscopic decompression of the orbital cavity. Authors are showing the method of operating curing on the basis of the case ill around thyroid orbithopathy in the course of illness Graves- of Basedow with accompanying diabetes.
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PMID:[Endoscopic decompresion of orbital cavity in the course of the Graves' ophthalmophaty]. 1900 63

The rate of oxygen consumption is an important parameter to assess the physiology of the human cornea. Metabolism of oxygen in the cornea is influenced by contact-lens-induced hypoxia, diseases such as diabetes, surgery, and drug treatment. Therefore, estimation of in vivo corneal oxygen-consumption rate is essential for gauging adequate oxygen supply to the cornea. Phosphorescence quenching of a dye coated on the posterior of a soft contact lens provides a powerful technique to measure tear-film oxygen tension (Harvitt and Bonanno, Invest Ophthalmol Vis Sci 1996;37:1026-1036; Bonanno et al., Invest Ophthalmol Vis Sci 2002;43:371-376). Unfortunately, previous work in establishing oxygen-consumption kinetics from transient postlens tear-film oxygen tensions relies on the simplistic assumption of a constant corneal-consumption rate. A more realistic model of corneal metabolism is needed to obtain reliable oxygen-consumption kinetics. Here, physiologically relevant nonlinear Monod kinetics is adopted for describing the local oxygen-consumption rate, thus avoiding aphysical negative oxygen tensions in the cornea. We incorporate Monod kinetics in an unsteady-state reactive-diffusion model for the cornea contact-lens system to determine tear-film oxygen tension as a function of time when changing from closed-eye to open-eye condition. The model was fit to available experimental data of in vivo human postlens tear-film oxygen tension to determine the corneal oxygen-consumption rate. Reliance on corneal oxygen diffusivity and solubility data obtained from rabbits is no longer requisite. Excellent agreement is obtained between the proposed model and experiment. We calculate the spatial-averaged in vivo human maximum corneal oxygen-consumption rate as Q(c)(max) = 1.05 x 10(-4) mL/(cm(3) s). The calculated Monod constant is K(m) = 2.2 mmHg.
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PMID:Diffusion and Monod kinetics to determine in vivo human corneal oxygen-consumption rate during soft contact-lens wear. 1908 56

Chemical lead 2 (CL2) is the first non-sphingosine-1-phosphate (Sph-1-P) analog type antagonist of endothelial differentiation gene-1 (Edg-1/S1P(1)), which is a member of the Sph-1-P receptor family. CL2 inhibits [(3)H]Sph-1-P/S1P(1) binding and shows concentration-dependent inhibition activity against both intracellular cAMP concentration decrease and cell invasion induced by the Sph-1-P/S1P(1) pathway. It also inhibits normal tube formation in an angiogenesis culture model, indicating that CL2 has anti-angiogenesis activity. This compound improved the disease conditions in two angiogenic models in vivo. It significantly inhibited angiogenesis induced by vascular endothelial growth factor in a rabbit cornea model as well as the swelling of mouse feet in an anti-type II collagen antibody-induced arthritis model. These results indicate that the Sph-1-P/S1P(1) pathway would have an important role in disease-related angiogenesis, especially in the processes of migration/invasion and tube formation. In addition, CL2 would be a powerful tool for the pharmacological study of the mechanisms of the Sph-1-P/S1P(1) pathway in rheumatoid arthritis, diabetes retinopathy, and solid tumor growth processes.
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PMID:Involvement of sphingosine-1-phosphate and S1P1 in angiogenesis: analyses using a new S1P1 antagonist of non-sphingosine-1-phosphate analog. 1915 Jun 9

Long-term duration of lifestyle-related diseases including diabetes induces various ocular diseases. For this reason, the development of lifestyle-related ocular diseases is closely related to the aging process. In the present study, we tried to reveal the molecular mechanism of lifestyle-related ocular diseases, especially diabetic complications of the eyes, in relation to aging. To unify the molecular mechanisms of diabetic complications and aging changes of the eyes, we focused on two kinds of nonenzymatic post-translational modification products: advanced glycation end products (AGEs) and D-amino acids. We found that the accumulation of proteins rich in AGEs and D-amino acids plays a central role in the development of both diabetic complications and such changes of the eyes as diabetic retinopathy, diabetic keratopathy, pinguecula, spheroidal degeneration of the cornea, and drusen. In addition, decreased function in AGE-modified and D-amino acid-containing proteins is a factor in the development of diabetic complications and aging changes in eyes. In this way, posttranslational changes in molecules and amino acids are important contributing factors in the development of diabetic complications and aging changes in eyes. In conclusion, accumulation of AGE-modified and D-amino acid-containing proteins is the molecular mechanism of both diabetic complications and the aging changes in eyes.
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PMID:[Ocular diseases caused by accumulation of proteins with post-translational modifications]. 1934 86

Patients with diabetes are at increased risk for developing corneal disorders, termed diabetic keratopathy. Treatments for diabetic keratopathy are limited. Preclinical studies have demonstrated that topical administration of either naltrexone (NTX) or insulin (INS) accelerates corneal re-epithelialization in type I diabetic rats. This study determined whether the combination of NTX and INS would have additive effect(s) on the re-epithelialization of corneal abrasions in diabetic male Sprague-Dawley rats beyond either agent alone. Type 1 diabetes (DB) (glucose levels>400mg/dl) was induced with streptozotocin; glycemic levels were not controlled with INS. Eight weeks after induction of diabetes, a 5mm diameter circular abrasion was created in the center of the cornea in one eye of each rat. Eye drops (0.05ml) of INS [1U ( approximately 6nM)] and NTX (10(-5)M) in Vigamox were administered separately 4 times daily for 7 days (NTX/INS); DB control rats received drops of sterile vehicle (DB SV) 4 times daily. Two other groups of rats were given only NTX (DB NTX) or only INS (DB INS). Re-epithelialization was monitored by fluorescein staining, and images were recorded with a CCD camera. Areal measurements were made using Optimas software, and the percentage of epithelial defect over a 40h period was calculated. Twenty-four hour after formation of an abrasion ( approximately 21.7+/-0.4mm(2)area), corneal wounds in DB rats treated with NTX, INS, or NTX/INS were significantly smaller (p<0.001) than those in DB SV rats, with reductions in the size of the defect ranging from 24 to 84%. DB rats treated with NTX or INS alone also were observed to have reductions in wound size of 22 and 29%, respectively, from subjects in the DB SV group at 16h. At 16h both the DB NTX and DB INS groups had defects that were 13 and 27%, respectively, smaller than those for the DB NTX/INS group, and at 40h the DB INS animals had 78% smaller corneal wounds than in the DB NTX/INS group. Therefore, the DB NTX/INS group exhibited some slight delays in wound repair compared to the DB NTX and DB INS groups. Topical application of NTX and/or INS to the cornea had no effect on non-invasive measures that included ocular morphology, intraocular pressure, or corneal thickness. These data demonstrate that although NTX or INS accelerates wound healing, concomitant application of NTX and INS to corneal abrasions in diabetic animals does not have an additive effect on re-epithelialization.
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PMID:Naltrexone and insulin are independently effective but not additive in accelerating corneal epithelial healing in type I diabetic rats. 1957 13

The opioid growth factor (OGF)-OGF receptors (OGFr) axis plays an important role in the homeostasis and re-epithelialization of the mammalian cornea. This tonically active growth regulatory inhibitory pathway is involved in cell replication, and the endogenous neuropeptide OGF targets cyclin-dependent kinase inhibitors, p16 and/or p21. Blockade of OGF-OGFr interfacing by systemic or topical administration of opioid antagonists such as naltrexone (NTX) results in accelerated DNA synthesis, cell replication, and tissue repair. Molecular manipulation of OGFr using sense constructs delayed corneal re-epithelialization, whereas antisense constructs accelerated repair of the corneal surface. Corneal keratopathy, a significant complication of diabetes mellitus, is manifested by delays in corneal re-epithelialization following surgery, injury, or disease. Tissue culture studies have shown that addition of NTX stimulates DNA synthesis and explant outgrowth of rabbit corneal epithelium, whereas OGF depresses DNA synthesis and explant outgrowth in a receptor-mediated manner. NTX accelerated corneal re-epithelialization in organ cultures of human and rabbit cornea. Systemic application of NTX to the abraded corneas of rats, and topical administration of NTX to the injured rabbit ocular surface, increased re-epithelialization. Systemic injections or topical administration of NTX facilitates re-epithelialization of the cornea in diabetic rats. Given the vital role of the corneal epithelium in maintaining vision, the frequency of corneal complications related to diabetes (diabetic keratopathy), and the problems occurring in diabetic individuals postoperatively (e.g., vitrectomy), and that conventional therapies such as artificial tears and bandage contact lenses often fail, topical application of NTX merits clinical consideration.
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PMID:Diabetic keratopathy and treatment by modulation of the opioid growth factor (OGF)-OGF receptor (OGFr) axis with naltrexone: a review. 1968 62


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