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)

Neuropathological examination of bladder biopsies was done on 14 patients with severe insulin-dependent adult-onset diabetes and compared with the acetylcholinesterase and S100 staining of 38 control specimens. A decrease in acetylcholinesterase activity, due to axonal degeneration was found in all cases. An increase in S100 positivity was found in the majority and is due to Schwann cell proliferation as a regeneration attempt after demyelination or axonal degeneration. When acetylcholinesterase activity decreases and an S100 density increase is found in a patient with diabetes, this combination is highly suggestive of thorough diabetic cystopathy amenable to early symptomatic treatment.
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PMID:Diabetic cystopathy: neuropathological examination of urinary bladder biopsies. 306 36

Necrobiosis lipoidica diabeticorum is an unusual dermatologic condition with a characteristic clinical appearance and a clear association with diabetes mellitus. There is currently no treatment that reverses the atrophic changes associated with this lesion. We have carried out a clinicopathologic study on 15 subjects and, in addition, have reviewed 10 further biopsy specimens of necrobiosis lipoidica diabeticorum. We found a frequent association of necrobiosis lipoidica diabeticorum with other chronic complications of diabetes mellitus, including limited joint mobility. It is possible that nonenzymatic glucosylation or other changes in collagen may be important in the etiology of necrobiosis lipoidica diabeticorum and the limited joint mobility. We confirmed that cutaneous anesthesia is usually present in the necrobiosis lipoidica diabeticorum lesions. With the use of an antibody to S100 protein and an immunohistochemical method, there was an apparent decreased number of nerves in the skin lesions. We suggest that sensory loss results from local destruction of cutaneous nerves by the inflammatory process. Finally, in six elliptical biopsies extending into clinically normal skin, we demonstrated that the inflammatory infiltrate of necrobiosis lipoidica diabeticorum extended from the lesion into apparently normal skin surrounding clinically active lesions. Thus, intradermal steroids might be administered to perilesional areas surrounding active lesions in the hope of halting progression.
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PMID:Necrobiosis lipoidica diabeticorum: a clinicopathologic study. 335 Oct 15

A solitary massive tumor developed in the left eye of a 61-year-old female who had a history of insulin-independent diabetes mellitus for 20 years and whose left eye had become blind due to repeated anterior uveitis in the recent several years. The eyeball was enucleated and used for further examinations. Intraocular tissues were widely infiltrated by histiocytes, though no extraocular invasion or further metastasis was found. Histological examination including alpha 1-anti-chymotrypsin and S100 staining revealed the features characteristic of histiocytosis X. This is probably a case of intraocular histiocytosis X with no evidence of systemic symptoms.
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PMID:[A case of intraocular histiocytosis X]. 833 72

Calcium receptor proteins are an essential link between hormones that alter intracellular calcium levels and the generation of cellular responses. However, there is no information available regarding the role of calcium receptor proteins, in particular the S100 family, in insulin action and/or diabetes. This study examines the effects of streptozotocin-induced type I diabetes on the expression of the individual S100A1 and S100B isoforms as well as their binding proteins. Diabetes did not increase (or initiate) S100B expression in any non-S100B-expressing tissue (skeletal muscle, heart, kidney, liver, spleen, and pancreas). In all S100B-expressing tissues examined (brain, white fat, and testes), S100B protein levels increased approximately 2-fold while steady state S100B messenger RNA (mRNA) levels decreased. S100A1-expressing tissues exhibited increased (kidney and lung), decreased (skeletal muscle), and unchanged (brain and heart) S100A1 protein levels. While noncoordinate changes in S100A1 protein and steady state mRNA levels were observed in heart, other S100A1-expressing tissues (brain, slow twitch skeletal muscle, and kidney) exhibited coordinate changes in S100A1 protein and steady state mRNA levels. Altogether, these results suggest that the effects of diabetes on S100 expression are isoform as well as tissue-specific. Gel overlay analysis of the S100-binding protein profile revealed both increases and decreases in binding proteins in all tissues examined. In summary, changes in the expression of S100A1, S100B, and S100-binding proteins occur in type I diabetes and represent important molecular events in the effects of insulin/insulin insufficiency on cell function.
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PMID:S100A1 and S100B expression and target proteins in type I diabetes. 938 98

S100 proteins (16 members) show a very divergent pattern of cell- and tissue-specific expression, of subcellular localizations and relocations, of post-translational modifications, and of affinities for Ca2+, Zn2+, and Cu2+, consistent with their pleiotropic intra- and extracellular functions. Up to 40 target proteins are reported to interact with S100 proteins and for S100A1 alone 15 target proteins are presently known. Therefore it is not surprising that many functional roles have been proposed and that several human disorders such as cancer, neurodegenerative diseases, cardiomyopathies, inflammations, diabetes, and allergies are associated with an altered expression of S100 proteins. It is not unlikely that their biological activity in some cases is regulated by Zn2+ and Cu2+, rather than by Ca2+. Despite the numerous putative functions of S100 proteins, their three-dimensional structures of, e.g., S100B, S100A6, and S100A7 are surprisingly similar. They contain a compact dimerization domain whose conformation is rather insensitive to Ca2+ binding and two lateral alpha-helices III and III, which project outward of each subunit when Ca2+ is bound. Target docking depends on the two hydrophobic patches in front of the paired EF-hand generated by the binding of Ca2+. The selectivity in target binding is assured by the central linker between the two EF-hands and the C-terminal tail. It appears that the S100-binding domain in some target proteins contains a basic amphiphilic alpha-helix and that the mode of interaction and activation bears structural similarity to that of calmodulin.
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PMID:New perspectives on S100 proteins: a multi-functional Ca(2+)-, Zn(2+)- and Cu(2+)-binding protein family. 1019 1

Receptor for advanced glycation end products (RAGE) is a multiligand member of the immunoglobulin superfamily of cell surface molecules whose repertoire of ligands includes advanced glycation end products (AGEs), amyloid fibrils, amphoterins and S100/calgranulins. The overlapping distribution of these ligands and cells overexpressing RAGE results in sustained receptor expression which is magnified via the apparent capacity of ligands to upregulate the receptor. We hypothesize that RAGE-ligand interaction is a propagation factor in a range of chronic disorders, based on the enhanced accumulation of the ligands in diseased tissues. For example, increased levels of AGEs in diabetes and renal insufficiency, amyloid fibrils in Alzheimer's disease brain, amphoterin in tumors and S100/calgranulins at sites of inflammation have been identified. The engagement of RAGE by its ligands can be considered the 'first hit' in a two-stage model, in which the second phase of cellular perturbation is mediated by superimposed accumulation of modified lipoproteins (in atherosclerosis), invading bacterial pathogens, ischemic stress and other factors. Taken together, these 'two hits' eventuate in a cellular response with a propensity towards tissue destruction rather than resolution of the offending pathogenic stimulus. Experimental data are cited regarding this hypothesis, though further studies will be required, especially with selective low molecular weight inhibitors of RAGE and RAGE knockout mice, to obtain additional proof in support of our concept.
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PMID:The biology of the receptor for advanced glycation end products and its ligands. 1110 54

Diabetes mellitus begins as a disorder of glucose metabolism that progressively compromises the function of virtually every organ system as the secondary complications inexorably develop. The quality of life for patients with diabetes is diminished by the consequences of these complications. Accelerated and aggressive atherosclerosis is the greatest cause of morbidity and mortality with diabetes, emphasizing the importance of determining underlying mechanisms. This review highlights the role of the multiligand receptor for advanced glycation endproducts (RAGE) and two of its ligands, advanced glycation endproducts (AGEs) and S100/calgranulins, in the pathogenesis of atherosclerosis associated with diabetes. The results of the studies reviewed herein suggest that RAGE is a potential therapeutic target for macrovascular disease in diabetes.
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PMID:Atherosclerosis and diabetes: the RAGE connection. 1112 75

RAGE is a multiligand member of the immunoglobulin superfamily of cell surface molecules whose properties extend the paradigm of ligand-receptor interactions. The receptor recognizes families of ligands with diverse structural features, such as advanced glycation endproducts (AGEs), amyloidogenic peptides/polypeptides, amphoterins, and S100/calgranulins rather than individual species. Engagement of RAGE by its ligands upregulates the receptor and initiates a cycle of sustained cellular perturbation; increased levels of RAGE on the cell surface make it an ideal target for subsequent ligand interactions and for propagating cellular dysfunction. At this time, the only means known to break this apparently vicious cycle appears to be blocking access to RAGE or removing the ligands. Taken together, these data suggest that RAGE has the potential to function as a progression factor in a range of disorders (AGEs are relevant to diabetes and other settings of oxidant stress, amyloidogenic peptides are relevant to amyloidoses, S100/calgranulins are relevant to inflammatory disorders, etc.) in which its ligands accumulate. The chronic juxtaposition of ligand and receptor triggers sustained cellular perturbation favoring mechanisms eventuating in tissue injury rather than those that would restore homeostasis.
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PMID:RAGE: a multiligand receptor contributing to the cellular response in diabetic vasculopathy and inflammation. 1112 4

Receptor for advanced glycation end-products (RAGE), and two of its ligands, AGE and EN-RAGEs (members of the S100/calgranulin family of pro-inflammatory cytokines), display enhanced expression in slowly resolving full-thickness excisional wounds developed in genetically diabetic db+/db+ mice. We tested the concept that blockade of RAGE, using soluble(s) RAGE, the extracellular ligand-binding domain of the receptor, would enhance wound closure in these animals. Administration of sRAGE accelerated the development of appropriately limited inflammatory cell infiltration and activation in wound foci. In parallel with accelerated wound closure at later times, blockade of RAGE suppressed levels of cytokines; tumor necrosis factor-alpha; interleukin-6; and matrix metalloproteinases-2, -3, and -9. In addition, generation of thick, well-vascularized granulation tissue was enhanced, in parallel with increased levels of platelet-derived growth factor-B and vascular endothelial growth factor. These findings identify a central role for RAGE in disordered wound healing associated with diabetes, and suggest that blockade of this receptor might represent a targeted strategy to restore effective wound repair in this disorder.
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PMID:Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. 1148 96

Receptor for AGE (RAGE), a member of the immunoglobulin superfamily, was first identified as a specific cell surface interaction site for Advanced Glycation Endproducts, or AGEs. AGEs, the products of nonenzymatic glycation/oxidation of proteins/lipids, accumulate in natural aging and disorders such as diabetes, renal failure and amyloidoses. Interaction of AGEs with RAGE has been linked to chronic inflammatory and vascular dysfunction that characterizes the chronic complications of these disorders. Recent studies have indicated that RAGE is a multiligand receptor, serving as a specific cell surface, signal transducing receptor for amphoterin, a molecule with implications for neurite outgrowth in neuronal development and in tumor cell proliferation and spread. RAGE is also a receptor for amyloid-beta peptide, whose interaction with neuronal and microglial RAGE within the CNS is linked to sustained inflammation and neuronal toxicity and cell death. RAGE also serves as a signal-transducing receptor for EN-RAGEs, and related members of the S100/calgranulin family of proinflammatory cytokines; consequences of this interaction include initiation and propagation of inflammatory responses. Consistent with an important role for ligand-RAGE interaction in these settings, blockade of RAGE suppresses chronic cellular activation and dysfunction in murine models of diabetic complications, inflammation and tumor proliferation and metastasis. Taken together, an new paradigm is emerging which links RAGE, a gene encoded within the Major Histocompatibility Complex (MHC) Class III regions, to central host response mechanisms in homeostasis and chronic disease.
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PMID:Receptor for age (RAGE) is a gene within the major histocompatibility class III region: implications for host response mechanisms in homeostasis and chronic disease. 1157 72


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