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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glycosaminoglycan (GAG) composition of a number of large and medium-sized arteries was studied in 6 alloxan-diabetic beagles and was compared with 6 normal, age-matched controls. Diabetic animals were maintained on diet and insulin for 100 days. The aortic arch, thoracic and abdominal segments, external iliac, superior mesenteric, renal, common carotid and coronary arteries were analyzed for hyaluronic acid (HA) and for heparan (HS), dermatan (DS), and chondroitin (CS) sulphates. All diabetic dogs displayed significant alterations. The HA content was reduced in iliac arteries, and together with HS, also in the thoracic aorta. HS or CS were increased in carotid, iliac and renal arteries, DS, a GAG constitutent with very high affinity for low density lipoproteins, was significantly increased in coronary arteries alone. 2 additional animals which are excluded from this series did not become diabetic after alloxanization and showed no change in arterial GAG content. Early changes in the chemistry of the arterial ground substance seem to provide a clue to the precocious development of atherosclerotic disease in diabetes.
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PMID:Arterial glycosaminoglycans in diabetic dogs. 739 10

Alterations in the connective tissue of the arterial wall have been suggested to play a role in the development of macrovascular disease in diabetes mellitus. The present study deals with changes in the content of GAG in aortic tunica media in human diabetes by separately analysing normal areas and areas with fibrous plaques. The thoracic aorta from 15 diabetic patients (7 with IDDM, 8 with NIDDM), and 30 sex- and age-matched non-diabetic subjects were collected at autopsy. Tunica intima was removed and GAG were isolated from the dried defatted and pulverized tunica media. GAG were quantified by uronic acid analysis and characterized by electrophoresis on cellulose acetate. Results showed that IDDM patients had a relative and absolute increase in hyaluronic acid in normal tunica media compared to non-diabetic subjects. There was a significant positive correlation between hyaluronic acid content of normal tunica media and duration of diabetes, but not between hyaluronic acid content and age. When tunica media from plaque areas was compared to normal areas the same pattern was evident in diabetic patients as in non-diabetic patients--significantly increased proportion of dermatan sulphate and reduced hyaluronic acid. The data agree with the notion that the arterial wall is subject to different pathological processes in diabetes, one of classical atherosclerosis with changes in GAG similar to non-diabetic subjects, and the other seen in areas without plaques with dissimilar alterations in GAG. These data therefore support the concept of the presence of a macrovascular disease in diabetes different from atherosclerosis.
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PMID:Glycosaminoglycans in the human aorta in diabetes mellitus: a study of tunica media from areas with and without atherosclerotic plaque. 817 43

In the present study, we have compared and analyzed published data related to the pathogenesis of the large vessel disease in diabetes. The prevailing opinion appears to be that diabetes accelerates the mechanism that leads to the development of classical atherosclerosis. However, as an alternative, we have amassed data that point to the presence of a diabetic macroangiopathy. This phenomenon comprises a constellation of nonatherosclerotic large vessel abnormalities. Today, we know that accumulation of periodic acid-Schiff (PAS)-positive material, as laminin, fibronectin, and type IV collagen, occurs together with hyaluronic acid and various types of connective tissue and calcium deposition. All these changes occur independent of the presence of atherosclerosis in the large vessels of diabetic patients. It seems to us that these observations emphasize that the concept of a specific diabetic macroangiopathy is a more fruitful working hypothesis than the usual theory of a link between atherosclerosis and diabetes. It provides a causal relationship (although the mechanism is unknown) between such changes and the abnormal metabolism in diabetes and a background for research strategy and tactics, aiming finally at the possibility of prevention and/or treatment of this common and dangerous disease.
Diabetes 1996 Jul
PMID:Diabetic macroangiopathy and atherosclerosis. 867 3

Alteration of the distribution pattern and composition of glycosaminoglycans (GAG) and proteoglycans may play an important role in the development of autoimmune diseases. Recent experiments indicate that anti-DNA antibodies cross-reacting with hyaluronic acid, heparan sulphate and chondroitin sulphate are present in patients with systemic lupus erythematosus. Furthermore, elevated hyaluronic acid antibody levels correlating with the disease score have been found in the sera of patients with autoimmune thyroid disease in comparison to controls. In vitro, T lymphocytes from patients with this disease increased the production of hyaluronic acid by cultured human retro-orbital fibroblasts. Fibroblast stimulation, as well as elevated collagen and GAG production, could be shown in chicken cell lines which spontaneously develop an autoimmune syndrome analogous to human scleroderma. To analyse the structure and distribution pattern of different GAG compounds in the tissues and body fluids of patients with autoimmune diseases a highly specific HPLC method was developed, which revealed increased urinary chondroitin sulphate and dermatan sulphate concentrations in patients with autoimmune thyroid disease in comparison to controls, concentrations which were positively correlated with disease severity and disease activity. Furthermore, the renal GAG excretion in patients with autoimmune diabetes mellitus was studied, and markedly higher excretion in patients compared to healthy controls was found, which was correlated with the duration of the disease and diabetic late complications. Thus, GAG polysaccharides not only appear to play a major role in the pathogenesis of autoimmune diseases, but have been successfully introduced as an activity marker of the disease.
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PMID:Glycosaminoglycans in autoimmunity. 882 50

Human serum contains several glycosaminoglycans (GAGs), mainly chondroitin sulphates and significantly less of heparan sulphate + heparin and dermatan sulphate. The non-insulin-dependent diabetes mellitus (with vascular complications) was associated with a significant increase in total serum GAG concentration, mainly of chondroitin sulphates and dermatan sulphate, with a simultaneous decrease in heparan sulphate + heparin level. These alterations were much more evident in patients with poor metabolic control. Hyaluronic acid (undetectable in healthy subjects and in patients with good metabolic control) appeared only in trace amounts in poorly controlled diabetic individuals. The obtained data allow to conclude that the diabetes mellitus-associated disturbances in tissue GAG metabolism lead to significant alterations in serum GAG composition.
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PMID:Glycosaminoglycans of human serum and their alterations in diabetes mellitus. 892 42

In order to analyse the immunological changes in patients with endocrine orbitopathy (EO) the antigenic character of orbital connective tissue was studied. Counter-stimulation assays of patients' lymphocytes with autologous retrobulbar fibroblasts resulted in a markedly increased lymphocyte proliferation in comparison to incubation with retrobulbar control fibroblasts. Proliferation tests of retrobulbar T cell lines showed significant responses to autologous retro-orbital connective tissue proteins, with molecular weights of 6-10 kD and 19-26 kD. Phenotypic analysis of orbital T cell lines indicates that they consisted predominantly of CD4+ cells. Hyaluronic acid production of orbital fibro blasts following co-cultivation with lymphocytes of EO patients or controls revealed a threefold increased synthesis in patients with EO. Furthermore, distribution pattern of orbital extracellular matrix glycosaminoglycans (GAG) differs in EO patients in comparison to controls. The results suggest the presence of autoreactive T cells directed against antigens of orbital fibroblasts, whose stimulation results in an augmented GAG synthesis in patients with EO.
Exp Clin Endocrinol Diabetes 1996
PMID:T cells and orbital connective tissue in endocrine orbitopathy. 898 Oct 8

We describe a premature aging disorder in a 15-year-old girl with severe growth and developmental deficiency. Her clinical findings included osteosarcoma, nuclear and subcapsular cataracts, insulin-resistant diabetes mellitus, osteoporosis, epilepsy, foot ulcers, erythroid macrocytosis, and unusual facial appearance. Hyaluronic acid levels in serum and urine were normal. Cultured skin fibroblasts had a normal potential for in vitro growth. This finding represents a new and unique premature aging syndrome.
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PMID:Premature aging syndrome with osteosarcoma, cataracts, diabetes mellitus, osteoporosis, erythroid macrocytosis, severe growth and developmental deficiency. 905 55

Membrana limitans interna retinae (MLI) has been studied since 1871 and in structure and composition have been discussed since then. With the use of electron microscopes when studying the MLI a new terminology has been introduced, i.e. the vitreoretinal border region (VBR). In this survey, ther general concept of basement membranes has been applied to the VBR. The VBR consists of two major components. The inner: anchoring fibrils of the vitreous body and the outer: MLI. The MLI is further defined as composed of three structures: the fusing points of the anchoring vitreous fibrils, lamina densa and lamina lucida. Stress forces between the retina and the vitreous body are transmitted via this border region, and may cause severe clinical conditions such as retinal detachment. To investigate this border region morphologically, improvements in the conventional preparation technique for scanning electron microscopy (SEM) were found to be necessary in order to exhibit more details of the VBR. A new rapid procedure for desiccating frozen resin-cracked retinal tissue using hexamethyldisilazane was found to be appropriate. Sixteen pairs of normal eyes, 16 pairs of monkey eyes, 55 pairs of non-normal eyes from different animal species, enzyme digested monkey retinas and the retinas of two rat models with diabetes and hypertension respectively were investigated. In addition to SEM, the vitreoretinal border region was also investigated by means of light microscopy and transmission electron microscopy. The material was analyzed morphometrically. The human MLI increases markedly in thickness during the first months/years of life in the equatorial and macular regions. The thickness is stable from the second decade, and remains unchanged throughout subsequent decades. A regional difference in thickness of the MLI was found in all human adult eyes and in monkey eyes; it was thickest in the macular region. The length of vitreous fibrils close to the MLI also varied between the four regions in human eyes, the longest being in the ora serrata region, the second longest in the equatorial region, the next longest in the optic disc region and the shortest in the macular region. A morphological similarity in the appearance of the VBR was found in humans and monkeys. All other animals, except for cephalopods, showed a marked uniformity of the VBR. The enzyme-digested monkey retinas showed the fibrillar meshwork of the VBR to consist mainly of collagen fibers surrounded predominantly by hyaluronic acid. No firm correlation between thickness of the VBR and diabetes or hypertension could be demonstrated in the two animal models.
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PMID:Morphology of the vitreoretinal border region. 929 70

The skin of rats with experimental (streptozotocin-induced) chronic diabetes mellitus exhibits significant decrease in glycosaminoglycans (GAGs) content. In the present study we asked the question whether the decrease in GAGs content is a result of decline in GAG biosynthesis or an increase in their degradation. We demonstrated by a pulse-labeling experiments that diabetes results in a decrease of [14C]-glucosamine incorporation into both hyaluronic acid and sulphated GAGs. During the chase period, there was no significant degradation of the pulse-labeled GAGs, suggesting that the reduction of GAGs content in the skin of diabetic rats is a result of decrease in GAG biosynthesis. Especially the biosynthesis of sulphated GAGs is deeply reduced. This phenomenon may be one of the factors which impairs the wound healing in diabetic subjects.
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PMID:Decreased biosynthesis of glycosaminoglycans in the skin of rats with chronic diabetes mellitus. 1033 65

Inflammatory destruction of insulin-producing beta cells in the pancreatic islets is the hallmark of insulin-dependent diabetes mellitus, a spontaneous autoimmune disease of non-obese diabetic mice resembling human juvenile (type I) diabetes. Histochemical analysis of diabetic pancreata revealed that mononuclear cells infiltrating the islets and causing autoimmune insulitis, as well as local islet cells, express the CD44 receptor; hyaluronic acid, the principal ligand of CD44, is detected in the islet periphery and islet endothelium. Injection of anti-CD44 mAb 1 hr before cell transfer of diabetogenic splenocytes and subsequently on alternate days for 4 weeks induced considerable resistance to diabetes in recipient mice, reflected by reduced insulitis. Contact sensitivity to oxazolone was not influenced by this treatment. A similar antidiabetic effect was observed even when the anti-CD44 mAb administration was initiated at the time of disease onset: i.e., 4-7 weeks after cell transfer. Administration of the enzyme hyaluronidase also induced appreciable resistance to insulin-dependent diabetes mellitus, suggesting that the CD44-hyaluronic acid interaction is involved in the development of the disease. These findings demonstrate that CD44-positive inflammatory cells may be a potential therapeutic target in insulin-dependent diabetes.
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PMID:Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody. 1061 10


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