Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The macromolecules of the intercellular matrix (MM) : collagen, elastin, proteoglycans and structural glycoproteins) are present in all tissues in variable amount and proportion. Some tissues, particularly rich in MM are designated as "connective tissues". Matrix macromolecules assure the integration of cells in tissues and of tissues in organs and in the whole organism. Differentiation, morphogenesis, maturation and aging are characterized by the variation of the raltiave rates of synthesis of individual MM-s. Several post-transcriptional and post-translational steps play an important role in biosynthesis of MM-S offering a multitude of possibilities for genetic and/or aquired anomalies. Recent progress in the descriptive and dynamic biochemistry of MM-s sheds new light on these anomalies which condition a whole class of diseases (the diseases of the intercellular matrix or matrix pathology). The molecular and cellular mechanisms of several of these diseases start to be understood. As the great majority of the important disease of occidental societies (such as vascular and articular diseases, diabetes, and the pathology of aging) belong to this category, intensive research in matrix biology and pathology as well as of its teaching in the medical curriculum should be considered as first priorities.
...
PMID:Matrix biology and pathology, a new branch of biomedical sciences. 86 48

Static lung pressure-volume curves, lung volumes, spirometry, diffusing capacity for CO, and airway and total pulmonary resistance were determined in 11 young men with juvenile-onset diabetes mellitus who were not cigarette smokers. Twelve nonsmoking men of similar age without diabetes served as control subjects. Elastic recoil at low lung volumes was significantly less in the diabetics than in the control group. Total lung capacity was also decreased in the diabetics. There were no significant differences between the 2 groups in the other parameters of pulmonary function measured. It is postulated that the abnormalities in lung elastic behavior are manifestations of the widespread elastin and collagen abnormalities that have been demonstrated in diabetes and are, in some respects, similar to those that occur during normal aging. Loss of elastic recoil at low lung volumes may cause more significant decreases in flows and gas transport as the juvenile diabetics age.
...
PMID:Abnormal lung elasticity in juvenile diabetes mellitus. 124 13

In this review, we have highlighted pivotal cellular and molecular events in the initiation and progression of atherosclerosis. Key components of lesion initiation are an enhanced focal intimal influx and accumulation of lipoproteins, including LDL in hemodynamically determined lesion-prone areas, focal monocyte-macrophage recruitment, intimal generation of ROS, and oxidative modification of lipoproteins (including LDL [Ox-LDL]). Modified lipoproteins are taken up by the non-downregulating macrophage scavenger receptor, with foam cell formation and the development of the so-called fatty streak. One transitional event in lesion progression is foam cell necrosis, likely attributable to the cytotoxicity of both intimal free radicals and Ox-LDL, with development of an extracellular metabolically inert lipid core. Another is the migration to and proliferation within the intima of medial SMCs, leading to the synthesis of plaque collagens, elastin, and proteoglycans. Mural thrombosis plays a significant role in the late-stage progression of lesions. Regression of lesions is considered a function of the dynamic balance among components of initiation, progression, plaque stabilization, and removal of plaque constituents--the so-called regression quartet. Here, we critically examine how components of diabetes mellitus might impact not only lesion development, but also lesion regression. It is concluded that some components of diabetes mellitus augment key mechanisms in lesion initiation and progression and will likely retard the processes of plaque regression. Specifically, we focus on the various influences of diabetes mellitus on lipoprotein influx and accumulation, free radical generation and Ox-LDL, monocyte-macrophage recruitment, thrombosis and impaired fibrinolysis, and the reverse cholesterol transport system. The importance of nonenzymatic protein glycosylation in modifying a number of these processes is emphasized.
Diabetes Care 1992 Sep
PMID:Pathogenesis of the atherosclerotic lesion. Implications for diabetes mellitus. 139 13

To clarify the therapeutic effects of several traditional Chinese medicines to improve disorders of carbohydrate, lipid and mineral metabolism, spontaneously diabetic rats (WBN/Kob) were treated with Vit. D2, 1 x 10(5) I.U./kg b.w./day, for 4 days, and then fed a hyperlipidemic diet containing traditional Chinese medicines for 6 weeks. The following results were obtained: 1) In the diabetic rats, the 3 traditional Chinese medicines further decreased the blood glucose level at 120 min after glucose loading in the glucose tolerance test. 2) The drugs increased the inorganic phosphate in the liver and normalized mineral metabolic disorder. 3) Hachimi-zio-gan decreased the cholesterol content in the kidney, and Sho-saiko-to decreased the cholesterol content in the elastin fraction (elastin-cholesterol) of the kidney. Such experimental results suggest that traditional Chinese medicines may be effective against the pathological conditions of diabetes mellitus that involve disorders of lipid and mineral metabolism.
...
PMID:[Effects of traditional Chinese medicines (dai-saiko-to, sho-saiko-to and hachimi-zio-gan) on spontaneously diabetic rat (WBN/Kob) with experimentally induced lipid and mineral disorders]. 144 86

All the living molecules appear to suffer from the deleterious effects of aging, but the primary mechanisms of this inexorable evolution are still unknown. In the case of proteins, two major types of chemical reactions participate in the aging phenomena: 1) structural transformations induced by the addition of radicals by enzymic or non-enzymic reactions, 2) proteolytic cleavages. Among the reactions of the first group, the nonenzymatic glycation is the more generalized, not only in diabetic patients but also in non diabetic subjects. This glycation depends on the probabilities of encounters between circulating glucose molecules and free amino groups existing either at the N-terminal end of the polypeptide chains or on the lysyl side chains. These reactions are more frequent in the extracellular spaces and connective tissues because glucose circulates freely in these spaces, because the level of glucose is better controlled inside the cells (and even lower in diabetes mellitus), and finally because the proteins of these regions, such as the collagens, fibronectin and elastin, are relatively long lived, even if their life-span is really shorter than it was precedently believed. The binding of sugar residues to protein amino groups determines frequent modifications of structure that often make the molecule inactive. For instance, when a glucose unit binds to a lysyl radical located in the active center of an enzyme, it suppresses the activity of this enzyme. More generally, in the case of the connective tissue proteins that participate in complex supramolecular assemblies, the presence of additional radicals on some ponctual locations may interfere with the correct association of molecules. This is particularly true for basement membranes whose structure is impaired in diabetes. Glycation might also introduce abnormal cross-links between polypeptides or modify the antigenic power of some proteins and explain the formation of autoantibodies. Another property of glycated proteins is their reaction with oxygen leading to the formation of superoxide. The binding of a reducing sugar on an amino function is followed by an Amadori rearrangement that forms a ketol group. Ketols groups have the property to transmit electrons to molecular oxygen, and to forming superoxide radicals. Superoxide is capable of degrading only one protein: collagen, but it is also able to transform itself into hydrogen peroxide and hydroxyl radicals, which are far more toxic than O2-. The result of the formation of these oxygen free radicals from glycated proteins is the initiation of the degradation of several types of proteins, like the collagens.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:[Aging mechanisms of proteins]. 165 Dec 60

The degradation of elastin during various pathological processes such as emphysema or arteriosclerosis was demonstrated by several investigators. In the present work, we adapted an ELISA technique for the determination of elastin peptide (EP) levels in human sera and plasma, in healthy and arteriosclerotic subjects. This test makes use of human aorta elastin hydrolyzed by a chemical procedure (kappa-elastin) instead of EP produced by pancreatic or leukocyte elastase. Polyclonal antibodies to this antigen were obtained in rabbits. The indirect ELISA procedure is sensitive, specific and reproducible. No correlation could be demonstrated between EP level and anti-EP antibody concentration of IgG or IgM types determined in the same serum samples. These antibodies did not interfere with EP determinations. EP concentration did not change with age in control subjects. In obliterative arteriosclerosis of the legs and in type IIb hyperlipoproteinemia, EP levels showed a marked increase, while in hypertension, ischemic heart disease and diabetes mellitus, the increase was moderate. In stroke, only slight changes were observed. In type IV hyperlipoproteinemia, EP levels were lower than in controls.
...
PMID:Determination of elastin peptides in normal and arteriosclerotic human sera by ELISA. 213 61

We studied lungs of spontaneously diabetic Bio-Breeding/Worcester (BB/W) Wistar rats which resemble human insulin-dependent diabetes mellitus. Compared with the age-matched control group, the body weight of the diabetic rats tended to be smaller and lung wet and dry weight were similar, but lung dry weight, relative to body weight and to lung wet weight, was significantly larger. Both air and saline lung volumes were reduced in the diabetic rats, and volume-pressure (V-P) curves expressed as a percent of maximal lung volume were significantly shifted downward and to the right of those in the control group over the midportion. Total DNA and RNA contents were similar in both groups, whereas protein content and concentration and protein/DNA and RNA/DNA ratios were significantly reduced in the diabetic rats. In contrast, content and concentration of 4-hydroxy-L-proline, elastin, and crude connective tissue were significantly higher in the diabetic group. We conclude that the increase in connective tissue proteins in the BB/W rats is most likely responsible for the shift in the V-P curves.
...
PMID:Lung mechanics and connective tissue proteins in diabetic Bio-Breeding/Worcester Wistar rats. 243 83

We adapted a highly sensitive and reproducible ELISA technique for the determination of anti-elastin peptide antibodies of IgG type AEAb-IgG) and IgM type AEAb-IgM) in human sera. The determination was performed in the sera of 265 normal and diseased persons. The pathologies studied included obliterative arteriosclerosis of the legs, ischemic heart disease, stroke, diabetes mellitus, type IIb and IV hyperlipoproteinemia and hypertension. No clearcut correlation could be found between AEAb and age. In contrast, in arteriosclerotic patients and especially in obliterative arteriosclerosis of the legs and ischemic heart disease, the concentration of AEAb-IgG was significantly increased. The AEAb-IgM showed no change in the studied diseases. Both types of AEAb were decreased in type IV hyperlipoproteinemia. Anti-elastin antibodies may be involved in the pathomechanisms of the above diseases and the determination of antibody concentrations may be of some help in obliterative arteriosclerotic diseases.
...
PMID:Determination of anti-elastin peptide antibodies in normal and arteriosclerotic human sera by ELISA. 264 31

In vivo lung connective tissue and DNA synthesis, following intraperitoneal injection of [14C]proline and [3H]thymidine, were studied in streptozotocin-induced diabetic rats fed ad libitum. Insulin-treated diabetic and normal rats similarly fed, and undernourished rats weight-matched to the untreated diabetics, served as comparison groups. The ratio of unbound [14C]hydroxyproline to total [14C]hydroxyproline in the lung was used to assess connective tissue degradation. Compared to the normal group, the untreated diabetic animals showed similar synthesis of collagen and elastin, reduced synthesis of total protein and DNA, and decreased degradation of connective tissue. When compared with the normal group, the undernourished animals showed diminished synthesis of total protein, collagen, elastin, and DNA, and increased degradation of connective tissue. In comparison to the undernourished group, the untreated diabetic animals indicated increased synthesis of collagen and elastin, and diminished degradation of connective tissue; total protein and DNA syntheses were similar. The insulin-treated diabetic animals showed increased collagen and DNA synthesis. We conclude that experimental diabetes has a profound effect on lung connective tissue metabolism, supporting previous observations of connective tissue abnormalities and morphometric changes. The increase in lung collagen and elastin in diabetes is in part due to reduced breakdown of the connective tissue proteins.
...
PMID:Experimental diabetes and the lung. II. In vivo connective tissue metabolism. 305 60

The elastin content of the aortic muscle and the elastase-like activity of the extracts of aortic muscle were studied in spontaneously diabetic BB rats and in rats made diabetic by a single bolus i.v. injection of alloxan. In both modes of diabetes, the total alkaline-insoluble aortic elastin content was significantly reduced in diabetic rats compared to that in the corresponding control rats. This reduction in aortic elastin was also accompanied by a consistent increase in the elastase-like activities of the aortic extracts prepared from the same tissues. Such a reciprocal relationship between aortic elastin content and elastase-like activity has previously been reported in rats with malignant hypertension. Since the rats used in this study were not hypertensive, the altered elastin metabolism observed in this work is likely to be a manifestation of diabetic disease and may in part account for the vascular changes associated with diabetes mellitus.
...
PMID:Alterations of elastin and elastase-like activities in aortae of diabetic rats. 319 Nov 58


1 2 3 4 5 6 7 8 9 10 Next >>