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)

Insulin seems to regulate the biosynthesis of proteoglycans in some tissues such as growth plate and glomeruli. The present investigation was undertaken to assess the ex vivo influence of insulin on proteoglycan metabolism in bones. Mandible and femur bones were used. Xiphoid cartilage was used as a control tissue of high glycosaminoglycan content. Diabetes was induced by 0.12 mg/g b.w. streptozotocin in male Sprague-Dawley rats, a number of which was treated with insulin (1 I.U./100 g b.w.) for 6 days. As compared with control animals, diabetic rats exhibited a decreased [35S]sulfate uptake as well as a shift to the right in Sephacryl S-500 chromatography. In addition, they showed lower density of proteoglycans in sucrose gradient and shorter glycosaminoglycan side chains in Sephadex G-200 chromatography. These changes were partly reversed by insulin.
 ...
PMID:Proteoglycans in bones of streptozotocin-induced diabetic rats. 224 27

Topical zinc is widely used in wound treatment although the beneficial effect of zinc has only been documented in zinc-deficient patients who were given zinc orally. The main purpose of this study was to investigate the effect of topically applied zinc on leg ulcer healing and examine its effect on some mechanisms in wound healing using standardized animal models. Additionally, absorption of zinc into wounds and intact skin treated topically with zinc was studied. In a double-blind trial involving 37 leg ulcer patients with low serum zinc levels, topical zinc oxide promoted cleansing and re-epithelialization. Infections and deteriorations of ulcers were less common in zinc oxide treated patients. Re-epithelialization, an important mechanism in the closure of leg ulcers, was enhanced with zinc oxide applied topically on partial-thickness wounds in pigs with normal zinc status. Zinc sulfate at three different concentrations did not, however, result in this beneficial effect on the resurfacing of wounds. The inflammatory reaction was diminished in zinc treated wounds except when a high zinc sulfate concentration was applied. Bacterial growth and concomitant diseases such as diabetes can complicate wound healing. In normal rats, bacterial growth in full-thickness wounds was reduced with topical zinc oxide but not in hyperglycemic diabetic rats. The anti-bacterial mechanism of zinc oxide seemed to be more indirect and to be mediated via local defense systems rather than being directly toxic to the bacteria. Healing of 21-day-old skin incisions was impaired in zinc deficiency, as measured by a significantly decreased wound breaking strength in zinc-deficient rats compared with that of pair-fed controls. The decreased breaking strength did not seem to be due to differences in collagen concentration of the wounds. Zinc oxide was slowly but continuously solubilized when applied on open wounds in rats. On the other hand, with zinc sulfate, the zinc concentrations, either locally or systemically, did not maintain a constant level for the 48-hour post-operative treatment period as they did with zinc oxide. Zinc absorption in and through normal human forearm skin was demonstrated after treatment with a zinc oxide medicated occlusive dressing by increased zinc levels in epidermis, interstitial fluid and dermis compared with the non-zinc control dressing. In conclusion, topical zinc may stimulate leg ulcer healing by enhancing re-epithelialization, decreasing inflammation and bacterial growth. When zinc is applied on wounds it not only corrects a local zinc deficit but also acts pharmacologically.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Studies on zinc in wound healing. 227 9

The metabolism of proteoglycans in normal growth plate and the changes in growth plate morphology induced by diabetes and malnutrition were studied in rats. The proteoglycans had a significantly faster turnover (half-life measured with [35S]sulfate labeling: 25-30 h) than the cells in the growth plate. Morphometric studies showed significant reductions of cell number, zone height, and [3H]thymidine incorporation in growth plates from rats with untreated streptozotocin-induced diabetes compared to normal rats. Similar, although less pronounced alterations were observed in malnourished, nondiabetic rats. Disaggregation and degradation of proteoglycans are probably necessary prerequisites for calcification. Our data indicate that the proteoglycans are in a dynamic state of rapid biosynthesis and degradation throughout the growth plate with a shift in the balance at the calcification front toward less synthesis and more degradation.
 ...
PMID:Kinetics of proteoglycans and cells in growth plate of normal, diabetic, and malnourished rats. 229 70

A 59-year-old woman, one of 5 cases with familial type III hyperlipoproteinemia reported at our clinic to date, had nephrotic syndrome and diabetes mellitus, but had neither coronary atherosclerosis nor xanthoma. A renal biopsy specimen revealed a massive cluster of foam cells containing apolipoprotein B and E in the mesangial region of the kidney. A restricted diet intake combined with lipid-lowering drugs such as cholestyramine, clinofibrate, and bezafibrate, in addition to methylprednisolone was not very effective in lowering serum triglyceride and cholesterol levels within physiological ranges. Therefore, plasmapheresis, using a dextran sulfate-cellulose column, was performed. Repeated plasmapheresis resulted in a marked decrease in both serum total cholesterol and triglyceride. A second renal biopsy specimen performed 2 years later revealed a marked reduction in foam cells with concurrent improvement in her nephrotic syndrome and glucose intolerance. These results suggest that familial type III hyperlipoproteinemia may be responsible for glomerular lipidosis resulting in nephrotic syndrome. They also indicate that plasmapheresis using a dextran sulfate-cellulose column is very effective in the removal of abnormal lipoproteins such as beta-very low density lipoprotein and intermediate density lipoprotein in a case of familial type III hyperlipoproteinemia.
 ...
PMID:Effects of plasmapheresis on familial type III hyperlipoproteinemia associated with glomerular lipidosis, nephrotic syndrome and diabetes mellitus. 231 Apr 24

The effect of alcohol on urinary glycosaminoglycan (GAG) and protein excretion was studied in one-month-old normal control C57BL/6J (CBL) and genetically diabetic (db/db) mice. Ethyl alcohol (4 g/kg) was given once a day by gavage for 58-64 days. Increased amounts of urinary total GAGs and protein were found in diabetic mice. Alcohol treatment increased urinary excretion of total GAGs, heparan sulfate and protein only in nondiabetic CBL but not in diabetic mice. Also, alcohol increased creatinine clearance only in CBL mice. The reason for the lack of effect of alcohol in diabetic mice is unknown. A significant positive linear relationship was found between urinary total GAG and protein concentrations. Possible significance of this relationship in diabetes is discussed.
 ...
PMID:Effect of alcohol on urinary glycosaminoglycan and protein excretion in normal and diabetic mice. 233 95

The effects of non-enzymatic glycation on heparin cofactor II activity, at glucose concentrations which might be expected in physiological or diabetic conditions have been evaluated in this study. Radiolabelled glucose incorporation was associated with a loss of heparin cofactor anti-thrombin activity. The heparin cofactor heparin and dermatan sulfate-dependent inhibition of thrombin was significantly reduced, showing a remarkable decrease of the maximum second order rate constant. This study shows that heparin cofactor can be glycated at glucose concentrations found in the blood, and that this phenomenon produces a loss of heparin cofactor-antithrombin activity. These data suggest, furthermore, a possible link between heparin cofactor glycation and the pathogenesis of thrombosis in diabetes mellitus.
 ...
PMID:Non-enzymatic glycation reduces heparin cofactor II anti-thrombin activity. 234 33

The basal laminae of capillaries, glomeruli, and nerves are thickened in diabetes. Previous studies have shown that diabetic tissues produce increased levels of basal lamina collagen and reduced levels of proteoglycans. Since heparan sulfate and chondroitin sulfate proteoglycans are thought to act as anionic barriers regulating passage of proteins across Bruch's membrane of the eye, the cationic electron microscope tracers, polyethyleneimine (PEI) and ruthenium red, were used to study the distribution of anionic sites in Bruch's membrane of spontaneously diabetic Bio-Breeding/Worcester (BB-W) rats and streptozotocin-diabetic rats. The distribution of the two tracers is similar. In Bruch's membrane of control rats, electron dense particles are present at regular intervals along both sides of the basal laminae of the retinal pigment epithelium (RPE) and of the choriocapillary endothelium (CE), and along collagen fibers in the zone between the two basal laminae. Within 3-6 months after the onset of hyperglycemia in both diabetic rat models, quantitative analysis shows a significant reduction in binding sites along both RPE and CE basal laminae, while thickness of both basal laminae is significantly increased. Because reductions in anionic binding sites along basal laminae in the renal glomerulus have been found to accompany changes in glomerular filtration, these changes suggest that filtration through Bruch's membrane is altered in diabetes.
 ...
PMID:Decreased anionic sites in Bruch's membrane of spontaneous and drug-induced diabetes. 243 30

Although prostaglandin E2 (PGE2) is known to inhibit glucose-induced insulin secretion, it is uncertain whether PGE2 actions on the beta-cell are direct, whether they are equipotent for both phases of hormone secretion, and whether the same mechanism of action prevails throughout. Study of the HIT cell, a clonal line of pancreatic beta-cells, provides answers to these questions because perifusion with glucose and 3-isobutyl-1-methylxanthine stimulates biphasic insulin secretion. Perifusion with PGE2 decreased both the first and second phases of glucose-induced insulin release to 47 +/- 4% of controls. Pretreatment with pertussis toxin partly prevented PGE2 inhibition to 80 +/- 4% of controls for first phase and 79 +/- 4% of controls for second phase. To evaluate whether the partial prevention of PGE2 inhibition seen with pertussis toxin pretreatment was caused by Gi heterotrimer association between the preincubation period and the end of perifusion, PGE2 actions were also examined during continuous treatment with pertussis toxin. Under these conditions, PGE2 inhibition of both phases was totally prevented. However, no difference was observed in membrane protein ADP ribosylation when cells were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after pretreatment or continuous treatment with pertussis toxin. Cyclic AMP (cAMP) accumulation was inhibited by PGE2 (from 3263 +/- 153 to 1549 +/- 158 fmol/10(6) cells) but less so after pretreatment with pertussis toxin (correlation between insulin release and cAMP accumulation during perifusion; n = 18, r = .85, P less than .001). Thus, PGE2 equally inhibits both phases of glucose-induced insulin secretion and cAMP generation through a pertussis toxin-sensitive G protein-mediated direct effect on the pancreatic beta-cell.
Diabetes 1989 Nov
PMID:Pertussis toxin-sensitive G protein mediation of PGE2 inhibition of cAMP metabolism and phasic glucose-induced insulin secretion in HIT cells. 248 18

The present study reported histochemical changes in alveolar bone glycosaminoglycans (GAG) (using Safranin O) and in interdental bone height in three groups of BB/W rats: diabetic, diabetes prone, and diabetes resistant. Safranin O staining intensity suggested that total GAG levels were highest in diabetic bone (p less than 0.05 compared to diabetes resistant, p less than 0.005 compared to diabetes prone) but not significantly different between diabetes prone and resistant groups. Following chondroitinase AC and ABC digestion, staining reactions suggested that the highest levels of dermatan sulfate were in the diabetes resistant group (p less than 0.001 compared to diabetic, p less than 0.001 compared to diabetes prone) and the highest levels of chondroitin sulfates were in the diabetes prone group (p less than 0.001). Coincidently the mean height of diabetes prone interdental septum was significantly less than that of diabetes resistant or diabetic groups (p less than 0.05). The study suggested that 1) diabetes and "prediabetes" produce significant changes in levels of chondroitin 4, 6, and dermatan sulfates within alveolar bone, 2) in "prediabetic" animals, interdental bone loss occurs prior to the onset of clinical symptoms and in the absence of local irritating factors, the bone height appears to return to normal levels, and 3) there may be a correlation between alveolar bone height and relative levels of dermatan sulfate.
 ...
PMID:Alveolar bone of BB/W rats: a morphometric and histochemical study. 248 88

Abnormalities in the incorporation of heparan sulfate proteoglycan into the glomerular basement membrane have been implicated in the pathogenesis of various proteinuric states, including diabetes mellitus. To understand further the interactions between proteoglycans and glomerular extracellular matrices, glomeruli were isolated from normal and streptozocin-induced diabetic rats after in vivo exposure to 35S-labeled sulfate and were treated with heparin in vitro. Heparin treatment released a unique heparan sulfate proteoglycan from glomerular cell surface or extracellular matrix proteoglycan receptors. Another, smaller heparan sulfate proteoglycan was the most abundant proteoglycan released into medium and was released constitutively in medium with or without added heparin. While the two heparin-extracted proteoglycans copurified on anion-exchange and gel-filtration chromatographic columns, they were resolved by composite 0.6% agarose--1.8% polyacrylamide gel electrophoresis. Glomeruli from diabetic rats contained decreased proportions of the heparin-releasable heparan sulfate proteoglycan and more constitutively released heparan sulfate proteoglycan. The apparent molecular weight and intrinsic charge of the heparin-released proteoglycan mixture and the apparent molecular weight and sulfation pattern of their 35S-labeled glycosaminoglycan chains after nitrous acid deaminative cleavage were similar in the two groups. A brief trypsin digestion of heparin-treated glomeruli released proportionately less integral membrane and extracellular matrix 35S-labeled proteoglycans and 35S-labeled glycopeptides from diabetic glomeruli than form control glomeruli. Elution of these 35S-labeled macromolecules from anion-exchange columns and migration in agarose-polyacrylamide gels were similar in the two groups. Abnormalities in proteoglycan-matrix interactions or proteoglycan processing may account for changes in the proportions of heparin- and trypsin-extracted proteoglycan compartments in diabetes.
Diabetes 1989 Jan
PMID:Release of glomerular heparan-35SO4 proteoglycan by heparin from glomeruli of streptozocin-induced diabetic rats. 252 Dec 10


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