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)

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.
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PMID:Abnormal lung elasticity in juvenile diabetes mellitus. 124 13

Combined biochemical and ultrastructural study of conjunctival biopsies of 27 normal subjects and 45 diabetics (40 to 60 years old) was made. The "in vitro" incorporation of 14C-glucosamine and 3H-proline in freshly excised conjunctival biopsies was studied. The alterations of the capillary basement membrane of the conjunctiva were studied by electron microscopy. The following results were obtained: 1) A decrease of the specific activity of 14C-glucosmaine incorporation was found in fractions of diabetic conjunctiva. 2) In diabetic conjunctiva the percentages of 3H-proline incorporation in polymeric collagen containing fraction and structural glycoproteins containing fraction were significantly increased with a parallel decrease of 3H-proline incorporation in "crude soluble collagen" fraction expressed as a percentage of total incorporation. 3) Significant thickening of capillary basement membrane was observed with the appearance of collagen-like fibrils within the basement membrane in diabetic conjunctiva. Such fibrils were not seen in normal basement membranes. A relation between the extent of basement membrane thickening and the appearance of collagen-like fibrils is suggested. 4) The higher percentage of incorporation of 3H-proline in polymeric collagen may be related to the appearance of collagen fibrils in thickened basement membranes of the diabetic conjunctival capillaries. 5) These results suggest an abnormal regulation of the relative rate of biosynthesis and/or excretion of intercellular matrix macromolecules (collagen, structural glycoproteins) as part of the metabolic disorders characterising diabetes.
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PMID:Biochemical and ultrastructural study of human diabetic conjunctiva. 126 6

The steady-state levels of mRNA encoding for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, basement membrane HSPG, and alpha 1(I) and alpha 1(III) collagen chains were examined in rat glomeruli at 4, 12, and 24 wk after injection of STZ. The mRNA levels for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly with age in the STZ-induced diabetic rats before morphological thickening of basement membrane occurred. In contrast, the mRNA levels for HSPG decreased markedly 4 wk after STZ injection and then increased with age compared with those for control rats. The mRNA levels for these ECM components showed a continuous decline with age in controls. Treating the diabetic rats with insulin for 4 wk ameliorated the abnormally regulated ECM gene expression in the glomeruli. These data suggest that the abnormal regulation of ECM gene expression in the glomeruli may contribute to the expansion of mesangial matrix and basement membrane thickening in diabetic rats, and that hyperglycemia may play a role in the abnormal ECM gene expression.
Diabetes 1992 Dec
PMID:ECM gene expression and its modulation by insulin in diabetic rats. 128 Feb 37

We studied the influence of fasting serum from nine insulin-dependent diabetic children and adolescents under insufficient metabolic control on normal human bone cells in vitro compared with serum from eight sex- and age-matched controls. Cell number 24 h after plating was significantly less under diabetic serum, indicating impaired cell attachment, spreading and initiation of cell proliferation. Cell number after five days was reduced by 1% diabetic serum, while higher serum concentrations had diverging effects on osteoblast proliferation. Collagen synthesis of human osteoblasts was significantly reduced by 8% diabetic serum compared to 8% control serum, while synthesis of non-collagenous proteins was not affected. Duration of diabetes (several weeks up to 12 years) had no influence on these parameters. The serum from one patient, which was studied a second time under excellent metabolic control three months later, however, had lost its inhibitory influence on collagen synthesis of osteoblasts. The pattern of the interstitial collagen types I, III and V was not altered by diabetic serum. These results indicate that defective regulation of proliferation and collagen synthesis of osteoblasts by components present in human diabetic serum may be an important factor in the development of diabetic osteopenia. The negative influence might be explained in part by reduced levels of IGF-I and elevated levels of IGF binding protein-1 in the diabetic sera.
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PMID:Defective stimulation of proliferation and collagen biosynthesis of human bone cells by serum from diabetic patients. 128 77

Diabetes mellitus is commonly associated with systolic and diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive controls, a heightened plasma insulin response to a glucose challenge is found consistently. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. Using the insulin/glucose clamp technique in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth-muscle cells. Physiological maneuvers, such as caloric restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; good evidence indicates that these maneuvers also can lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia also are associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate density and low-density lipoproteins, both of which are atherogenic. Last, insulin per se, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth-muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth-muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of a variety of growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including type II diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
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PMID:Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. 128 37

Twenty-nine IDDM patients with borderline hypertension were randomly allocated to placebo or nitrendipine treatment. Nitrendipine was given orally at a dosage of 20 mg once daily over 4 weeks. Stimulated platelet thromboxane formation at rest and after standardized, non exhausting exercise was measured by standard methods. In addition, plasma levels of platelet factor 4 and aggregation responses to collagen and ADP were determined. In the treatment group thromboxane formation after stimulation with collagen (0.3 and 1.0 micrograms/ml) and 1 mM arachidonic acid (AA) was reduced in the resting state. Exercise induced change of thromboxane synthesis in response to 1.0 micrograms/ml collagen was significantly lower as compared to placebo (p < 0.05). In parallel, PF4 plasma levels were significantly lowered (p < 0.05). Whole blood aggregation after collagen stimulation (1.0 micrograms/ml) was reduced after 4 weeks of nitrendipine treatment, but ADP (5 microM) induced aggregation was not. These effects of nitrendipine were not seen in platelet rich plasma. In conclusion long-term nitrendipine treatment may inhibit collagen dependent platelet activation in the blood of diabetic patients with borderline hypertension.
Diabetes Res 1992 Mar
PMID:Reduced platelet thromboxane formation after long-term administration of a dihydropyridine calcium channel blocker: a prospective, double-blind, placebo-controlled study with nitrendipine in borderline hypertensive patients with IDDM-type diabetes mellitus. 128 47

Patients with diabetes often develop complications involving collagen-containing connective tissues. Previous in vitro studies have demonstrated that glucose inhibits collagen fibril formation and subsequent cross-linking. Collagen with diminished cross-linking is more susceptible to collagenolytic degradation. This may underlie the decreased collagen levels. To test this hypothesis, D-glucose and its two analogs, L-glucose and 2-deoxy-D-glucose, were used in chick calvaria organ cultures to examine parameters of collagen metabolism. L-Glucose is not used by the cell and functions as an extracellular glucose-like molecule, while 2-deoxy-D-glucose inhibits normal D-glucose uptake by blockading the glucose transport mechanism. Each of these three sugars had the ability to inhibit collagen fibril formation. D-Glucose stimulated collagen synthesis; L-glucose had no effect; and deoxyglucose inhibited collagen synthesis. D-Glucose was able to reverse the inhibitory effect of deoxyglucose. D-Glucose did not change levels of degradation of newly synthesized collagen while both L-glucose and deoxyglucose stimulated collagen degradation. When glucose transport was inhibited by deoxyglucose, collagen degradation was further enhanced. We suggest that decreased collagen levels in the connective tissues of diabetics may result from a combination of inhibition of collagen fibril formation and subsequent cross-linking, as well as increased collagen degradation.
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PMID:Glucose and glucose analogs modulate collagen metabolism. 128 72

In our previous studies in experimental diabetic rats, we have observed close similarities of ultrastructure and accumulation of IgG and IgM between the mesangial expansion and arteriolar hyalinosis of the glomerulus, and have presumed that both diabetic lesions are essentially of similar nature. In the present study, we carried out a further study on the constituents of both these lesions, using the PA-TCH-SP-PD technique for neutral carbohydrates, sialic acid and glycoproteins and the IgG-gold-silver technique for type IV collagen and fibronectin. The above staining and immunolabelings proved to be comparable in both lesions of diabetic glomerulopathies. This argues for the hypothesis of the identity of the two lesions.
Diabetes Res Clin Pract 1992 Dec
PMID:Similarity of the constituents between glomerular arteriolar and mesangial lesions in experimental diabetes. 128 17

Renal disease is one of the most common and severe complications of diabetes mellitus. The hallmark of the disease, glomerulosclerosis, is characterized by an accumulation of extracellular matrix in the mesangial areas, leading to progressive obliteration of the vascular spaces. The role of the metabolic derangements of diabetes mellitus in the development of these lesions is incompletely understood. One of the consequences of hyperglycemia is the formation of advanced glycosylation end products (AGEs), which result from a series of rearrangements secondary to nonenzymatic reaction of glucose with proteins. Specific receptors for proteins modified by AGEs, present in several cell types, were recently described in human and rat mesangial cells. Furthermore, exposure of mesangial cells to AGEs was followed by an increase in fibronectin production. In the present study we show evidence that mouse mesangial cells exhibit an increase in collagen type IV mRNA and peptide synthesis after exposure to AGEs. Antibodies to AGE receptors prevent this increase, indicating that the response is AGE-receptor-mediated. In addition, anti-platelet-derived growth factor abrogates the AGE response, suggesting that platelet-derived growth factor acts as an intermediate factor. Transcription assay reveals that the elevated mRNA levels are due to an increase in the transcription rate, rather than to an increase in the stability of the message. Finally, the mRNAs coding for laminin and heparan sulfate proteoglycan are also increased after exposure to AGE, whereas glyceraldehyde 3-phosphate dehydrogenase mRNA levels remain constant. The increase in extracellular matrix mRNAs seen in the current study suggests that AGE formation in vivo may be one of the metabolic events leading to the development of diabetic glomerulosclerosis.
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PMID:Receptor-specific increase in extracellular matrix production in mouse mesangial cells by advanced glycosylation end products is mediated via platelet-derived growth factor. 131 71

Distribution of type IV collagen and laminin in the gingival capillary basement membrane from streptozotocin-induced diabetic rats was investigated using immunoelectron microscopy. Both type IV collagen and laminin were found throughout the basement membrane. Quantitative analysis revealed that the immunoreactive area for laminin did not change with age, and the width of laminin deposition remained constant, even when diabetes was induced in the animals. However, the immunoreactive area for type IV collagen thickened with age. Further, the width of type IV collagen in the basement membrane increased markedly 36 weeks after diabetes was induced. It was concluded that the thickening of the gingival capillary basement membrane in experimentally induced diabetic rats was due an increase of type IV collagen deposition.
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PMID:Immunohistochemical localization of type IV collagen and laminin in the gingival capillary basement membrane of the diabetic rat. 134 99


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