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

Recent concepts on the mechanisms of aging of extracellular matrix (EM) are reviewed as well as its involvement in age-associated diseases. Cell differentiation, histogenesis and organogenesis can be analyzed in terms of the program of the biosynthesis of EM macromolecules during development, maturation and aging. The most important biological role of EM is the integration of cells in tissues, of tissues in organs and of organs in the whole organism. EM can directly influence cell behavior through the contact between EM and the genome mediated by structural glycoproteins (fibronectin, laminin, elastonectin, etc.) interacting with other EM macromolecules (collagen, proteoglycans, elastin) and the cytoskeleton by trans-membrane receptors (integrins). Most age-associated diseases exhibit a deviation (qualitative or quantitative) from the normal program of EM biosynthesis. Three examples are analyzed in some detail: atherosclerosis, diabetes and malignant tumors. The degradation of elastic fibers catalyzed by cellular elastase-type enzymes is observed in atherosclerosis and also in emphysema and skin aging. Several of these enzymes were isolated and characterized from platelets, fibroblasts, smooth muscle cells and lipoproteins. The biosynthesis of some of them increases with age and facilitates cell migration. Plasma fibronectin increases with age exponentially. This increase is absent or strongly attenuated in diabetes and some cancers. Tissue fibronectin increases in diabetes, Werner syndrome and in the peritumoral desmoplastic reaction while most tumor cells can no more retain fibronectin on their membrane facilitating their movement in the organism. These examples demonstrate the importance of the study of cell matrix interactions for gerontology.
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PMID:Aging of the extracellular matrix and its pathology. 328 58

In order to further investigate the role of the immune system in the arteriosclerotic process, we investigated the anti-elastin peptide antibodies (AEAb) of the IgG and IgM types by DOT immunobinding assay in the sera of patients suffering from various arteriosclerotic diseases. In total 232 control and pathological sera were studied. In obliterative arteriosclerosis of the legs 90%, ischemic heart disease 67% and hypertension 60% of sera were positive for AEAb of the IgG type independent of age. In the case of diabetes mellitus, however, the duration of the disease was determinant. In rheumatoid arthritis, the results were negative. No clear-cut positivity could be demonstrated in stroke patients either. These results indicate that AEAb can be detected in some diseases and DOT appears to be an appropriate method for the AEAb screening in various diseases.
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PMID:Immunology of elastin: study of anti-elastin peptide antibodies by DOT immunobinding assay. 331 75

Diabetes induced by streptozotocin at 3 wk of age in rats resulted in diminished somatic growth by 7 wk of age. Specific lung volume and weight (volume or weight per 100 gram body weight) were increased. The amount of lung DNA was decreased, and collagen and elastin were increased. The volume proportion of alveolar walls was increased at the expense of alveolar air. Air spaces were diminished in size, and alveoli increased in number. Total phospholipids and disaturated phosphatidylcholine (DSPC) were decreased, but they were normal relative to alveolar surface area. These changes reverted towards normal as a result of insulin treatment. Rats matched in weight (undernourished animals) for the diabetic animals showed relative preservation of lung weight, increased DNA, and reduced nonconnective tissue protein, RNA, collagen, and elastin. Air spaces were enlarged, alveolar surface area was decreased, and alveoli were decreased in number. Total phospholipids and DSPC were decreased, but normal when expressed per alveolar surface area. We conclude that diabetes and undernourishment have different effects on connective tissue synthesis in the lung that affect lung growth and structure, providing further evidence for the "fishnet" hypothesis of alveolar growth.
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PMID:Experimental diabetes and the lung. I. Changes in growth, morphometry, and biochemistry. 333 58

Amyloid was isolated from islets of amyloidotic pancreata of monkey and human beings by solubilization of non-amyloid materials from the pancreas and digestion of contaminating collagen and elastin. The resulting pellet was estimated to be greater than 90% pure islet amyloid. Antibodies specific for monkey islet amyloid and for monkey and human liver amyloid A (AA) were raised in rabbits. Immunohistochemical reaction using the peroxidase antiperoxidase method demonstrated that amyloidotic pancreas reacted with both anti-AA and anti-islet amyloid antibodies. Although the antibodies are specific toward antigens, they cross-react with tissues from human and monkeys. The immunochemical results suggest the possibility that more than one kind of amyloid is associated with islet amyloidosis, but that a significant portion of the islet amyloid is related to AA. Preliminary chemical analysis indicated that islet amyloid is enriched with hexosamines while AA contains both hexosamines and hexoses. Establishment of the islet amyloid composition(s) can give insight into its source and its role in diabetes in Macaca nigra and human beings.
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PMID:Immunohistochemical study of islet amyloid in diabetes mellitus. 355 Jul 80

The biochemical and biomechanical properties of aortas from diabetic rats were investigated after a period of three months. Diabetes caused increased non-enzymatic glycosylation of lysine and hydroxylysine residues of collagen, whereas no changes were found in the reducible collagen cross-links. Although diabetes caused a reduction in the thickness of the aortic wall and a decrease in the dry weight and amount of collagen and elastin per mm2, no changes were found in the mechanical strength and stiffness of the wall. When the mechanical parameters were corrected for the decrease in dry weight, the tensile strength of the aortic wall was found to be increased compared with the control group. This increase in the stability of aortic collagen can be explained by formation of reactive carbonyl compounds from the glycosyllysines, resulting in stabile cross-links between the collagen molecules.
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PMID:Changes in collagen and elastin of the rat aorta induced by experimental diabetes and food restriction. 361 83

To elucidate the nature of the abnormality of elastin metabolism in arteriosclerosis, we determined the elastase-type activity in the human radial artery of patients with chronic renal failure due to glomerular disease and diabetes. Elastase-type activity was determined by HPLC analysis of the hydrolyzed products of succinyl-trialanine-4-nitroanilide, a sensitive synthetic substrate for elastase. Three kinds of hydrolyzed products, (L-Ala)2-NA, L-Ala-NA and NA, were found after incubation of the substrate with human radial artery in the presence of amastatin (an inhibitor of aminopeptidases). We assumed the activity that liberates NA to be an elastase-type activity because purified human aorta elastase liberates NA from the substrate. The pH optima of the human artery and rat aorta activities were 6.0 and 6.8, respectively. The elastase activity in human radial artery and rat aorta was inhibited by diisopropyl phosphofluoridate, a serine protease inhibitor, and by elastatinal, an elastase inhibitor. The elastase-type activity in the radial artery of patients with chronic renal failure was significantly lower than that of the control group, and the decrease was especially marked in the patients with juvenile onset diabetes. These results suggest that the elastin metabolism is abnormal in the radial artery in diseases that tend to cause atherosclerosis.
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PMID:Elastase-type activity in human radial artery in patients with chronic renal failure. 363 13

Ten patients with necrobiosis lipoidica lesions were studied. Five patients had diabetes mellitus. The age of the patients varied from 15 to 73 years and the duration of the skin lesions was from 2 to 20 years. Histologically, the lesions were characterized by degeneration of collagen and elastin. In some lesions elastin fibers could be seen in areas devoid of normal-looking collagen. Electron microscopy revealed loss of cross-striation of collagen fibrils and a marked variation in the diameter of individual collagen fibrils. The concentration of collagen, measured by assay of hydroxy-proline, a collagen-specific amino acid, was markedly decreased in the lesional skin, but the ratio of type I/III collagen was unchanged in the affected skin. Fibroblasts established from affected skin synthesized less collagen than cells derived from healthy-looking skin. The decreased collagen synthesis was due to a decreased amount of messenger RNA for type I procollagen, measured by hybridization with a specific human cDNA clone. The production of collagenase by these fibroblasts was not increased. Our results thus indicate that in necrobiosis lipoidica lesions, collagen fibrils are defective and the amount of collagen is reduced, probably due to decreased synthesis of collagen by affected fibroblasts.
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PMID:Necrobiosis lipoidica: ultrastructural and biochemical demonstration of a collagen defect. 380 59

Diabetes mellitus induces alterations in the metabolism of the macromolecules present in the intercellular matrices and particularly in the basement membranes. These contribute to the morphological changes characteristic of the disease : basement membrane thickening, skin thickening and induration. Accumulation of overglycosylated collagens and diminution of sulfated proteoglycan concentrations are the most generally reported biochemical modifications in human or animal diabetic states. More limited data are available concerning elastin, fibronectin and laminin in diabetes.
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PMID:Connective tissue in diabetes mellitus: biochemical alterations of the intercellular matrix with special reference to proteoglycans, collagens and basement membranes. 388 3

Elastic fibers are progressively lysed during maturation and aging and in an accelerated fashion in several aging diseases such as diabetes, arteriosclerosis, emphysema and several skin diseases. Several enzymes (elastase-type proteases) were isolated in recent years in our laboratory which appear to be involved in these processes. A cell membrane bound serine protease was isolated from arterial smooth muscle cells and was shown to increase with in vitro aging of the cells. A metallo-protease was isolated from skin fibroblasts and was shown to be capable of attacking the constituents of elastic fibers, mainly the microfibrillar glycoproteins and also the desmosine cross linked elastin in vivo. This partially purified fibroblast enzyme was shown to attack these elastic fibers when injected into the dermis. A new selective staining procedure was used to visualise and quantitate, by computerized image analysis, the skin elastic fibers in normal and pathological human or animal skin biopsies. This method, combined with the injection of elastase in rabbit skins, alone or together with inhibitors, enables the ex vivo/in vivo study of elastase action (and of its inhibition).
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PMID:Interaction between elastin and elastases and its role in the aging of the arterial wall, skin and other connective tissues. A review. 639 11

In studies concerning risk factors for cardiovascular diseases, a number of reports have emphasized the influence of lipids, but the role of dietary minerals other than sodium has been less studied. However, epidemiological studies have suggested that dietary intake of magnesium and potassium may be involved in such pathogenesis. Studies of the influence of magnesium deficiency on arteriosclerosis include its effect on the initial lesion, altered metabolism of elastin, proliferation of collagen, calcification, lipid metabolism, platelet aggregation and hypertension. Magnesium and potassium metabolism are closely related and magnesium is required for maintaining the level of cellular potassium. As a consequence, magnesium and potassium deficiency frequently occur together and potassium deficiency may be an aggravating factor in pathogenesis. The development of the initial lesion in the arterial wall may be facilitated by loss of cellular magnesium and potassium. Experimental magnesium deficiency induces arterial damage, a loss of magnesium and potassium and an increase in the calcium and sodium content of the cell. Experimental models that have been used to produce cardiovascular lesions induce similar changes and losses of major intracellular cations may affect the main metabolic processes of the cell. This report summarizes the experimental evidence that magnesium deficiency may affect several different stages involved in arteriosclerosis and that potassium deficiency may exacerbate this. Magnesium deficiency results in vascular calcification. Experiments indicate that elastin is the site of the initial calcification and the metabolism of elastin is altered. This vascular lesion then brings about an increase in the collagen content of the wall. Low magnesium status could probably affect this process by slowing collagen resorption and lead to an irreversible accumulation of connective tissue. Results showing a different distribution of the various types of lipoprotein during experimental magnesium deficiency strongly suggest that lipid exchange between the vessel walls and blood can be modified. Severe magnesium deficiency in weanling rats produces a marked hypertriglyceridemia, a decrease in the percentage of cholesterol transported by HDL lipoprotein and a reduction in LCAT activity. The decreased clearance of circulatory triglycerides appears to be the major mechanism contributing to hyperlipemia. Magnesium deficiency could therefore contribute to accumulation of vascular lipid. Magnesium and potassium depletion have also been reported in diabetes and the vascular implications of this should be considered.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of magnesium and potassium in the pathogenesis of arteriosclerosis. 639 44


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