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)

To examine the question of whether hyperglycemia per se can affect basement membrane synthesis, intact rat lenses, which produce basement membrane in vitro, were incubated for 24 h with radioactive proline or lysine and varying concentrations of glucose. Lens capsule basement membrane (LCBM) was subsequently purified and analyzed for radiolabel incorporation and for specific activities of proline, hydroxyproline, lysine, and hydroxylysine. [14C]-proline and lysine incorporation into LCBM was increasingly stimulated in incubations performed with 10 and 20 mM compared with 5 mM glucose. High glucose concentration increased the specific activity of proline and lysine but not hydroxyproline or hydroxylysine, and decreased the ratio of radioactive hydroxyproline to proline. Gel electrophoresis of radiolabeled LCBM prepared after high glucose incubation revealed increased radioactivity in serveral high-molecular-weight components corresponding with the major Coomassie-blue peptide bands. The results indicate that glucose stimulates LCBM synthesis, and suggest that this effect derives from increased production of noncollagenous components.
Diabetes 1982 Dec
PMID:Lens capsule basement membrane synthesis. Stimulation by glucose in vitro. 681 45

The author, diabetic for 33 yr, has used a novel technique for maintaining blood glucose (BG) in the 60-120 mg/dl range and HbA1c in the 3.95-6.4% range, thereby lowering serum triglycerides from 200+ to 29 mg/dl, cholestrol from 250+ to 130 mg/dl, and insulin dosage from 80 to 25 U/day. BG is patient-monitored six times a day with Dextrostix and Ames Eyetone reflectance colorimeter, modified for battery operation. BG levels over 115 mg/dl are corrected with Regular insulin, 0.5 U for every 15 mg/dl elevation above 100 mg/dl. BG levels below 85 are treated with one glucose tablet (Dextrosol) for every 15 mg/dl below 100 mg/dl. Usual preprandial split insulin doses are: 5 U Regular (R) + 5 U Ultralente (UL) about 50 min prebreakfast, 5R about 50 min prelunch, and 5R + 5UL about 50 min presupper. High protein diet limits carbohydrate to one bread exchange per meal, no simple sugars, no fruits. Caloric distribution is approximately 15% CHO, greater than or equal to 45% PRO, less than or equal to 40% fat. This diet eliminates postprandial BG elevation without the large doses of R that might cause severe hypoglycemia when meals are slightly delayed. Snacks are contraindicated unless covered by additional R. Meals may be skipped or taken at any time provided R is withheld or times as appropriate. Psychological and physiologic improvements experienced by the author and other patients are described. The method is recommended to investigators as a means for testing long-term effects of euglycemia on sequellae of insulin-dependent DM in humans.
Diabetes Care
PMID:Virtually continuous euglycemia for 5 yr in a labile juvenile-onset diabetic patient under noninvasive closed-loop control. 699 59

Glomerular basement membrane (GBM) was labeled in vivo by the injection of tracer amounts of tritiated proline into normal and streptozotocin-diabetic rats. Basement membrane biosynthesis and turnover were determined from the specific activities of proline and hydroxyproline in samples purified following osmotic lysis of glomeruli isolated 4 h to 12 days after injection. Peak radiolabeling of normal and diabetic GBM occurred within 24-48 h and 48-72 h, respectively, and, when corrected for differences in the serum proline specific activities, [3H]proline incorporation was greater in diabetic than in normal samples. In contrast to the subsequent time-dependent progressive decline in radiolabeling in basement membranes from normal animals, specific activities of proline and hydroxyproline in diabetic glomerular basement membrane did not change significantly over the same period of observation. Renal cortical mass and glomerular basement membrane collagen content were preserved in diabetic animals despite loss of body weight. The findings are compatible with prolongation of glomerular basement membrane turnover in experimental diabetes, and suggest that diminished degradation contributes to the accumulation of glomerular basement membrane that is characteristic of chronic diabetes.
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PMID:In vivo biosynthesis and turnover of glomerular basement membrane in diabetic rats. 703 63

In rats with chronic diabetes, the synthesis of glomerular basement membrane was investigated in vivo by injection of 3H-proline. Compared to the nondiabetic controls, the basement membrane synthesis was markedly raised. The formation of hydroxyproline as parameter for the synthesis of the collagen portion of the basement membrane increased to a somewhat greater extent than the incorporation of 3H-proline. Hydroxyproline formation and proline incorporation showed a close correlation with the blood sugar level in the diabetic rats.
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PMID:In vivo studies on basement membrane synthesis in diabetic and nondiabetic rats. 716 52

The biosynthesis of collagen and fibronectin molecules by cultivated glomerular epithelial or mesangial cells was studied at confluency using radioactive proline or lysine as precursors. Collagen represented 0.5% of the total protein synthesized by the glomerular epithelial cells. About 60% of this collagenous protein were associated to the cell layer, whereas about 40% were secreted into the culture medium. Two major collagenous polypeptides were observed with apparent molecular weights of 185K and 170K, and were identified as two gene products of type IV procollagen. They exhibited ratios of 3- to 4-hydroxyproline, of total hydroxyproline to proline, and of hydroxylysine to lysine characteristic of type IV procollagen. They were degraded by bacterial collagenase. The patterns of peptides obtained after digestion of the 185K and 170K chains of this type IV procollagen with pepsin and V8 protease were identical to those obtained after digestion of type IV procollagen chains purified from a murine tumor (EHS sarcoma). Finally. a purified antibody to type IV collagen specifically immunoprecipitated the collagenous protein produced by the glomerular epithelial cells. By contrast, the mesangial cells synthesized about 5% of collagenous protein. 90% of this collagen were secreted into the cultured medium, whereas about 10% remained associated to the cell layer. Type I, III and IV procollagens were synthesized by the mesangial cells. Fibronectin was found in the medium and cell layer of both epithelial and mesangial cells. Fibronectin molecules were identified by their resistance to bacterial collagenase, their susceptibility to pepsin digestion, and their specific adherence to collagen. It was composed of disulfide-linked peptides of 220K daltons. The data therefore demonstrate that: (a) the glomerular epithelial and mesangial cells synthesize fibronectin molecules and type IV procollagen in vitro; (b) the cultivated mesangial cells also synthesize type I and III collagens. The implications of these findings in certain pathological circumstances, such as diabetes mellitus, are now being investigated.
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PMID:Synthesis of collagen and fibronectin by glomerular cells in culture. 732 12

A graded sieving procedure was used to isolate glomeruli and tubules from renal cortex of men of premature age up to 80 years and of 4 patients suffering from Zellweger syndrome, congenital nephrotic syndrome, polycystic renal disease or diabetes mellitus. Glomerular and tubular basement membranes (GBM and TBM, respectively) were obtained with a detergent procedure. Purity of basement membrane preparations was controlled with light and electron microscopy and by estimating total phosphorus content. Amino acid and carbohydrate composition of the basement membranes were determined and statistically evaluated. Comparison of GBM and TBM from the same kidneys showed at all ages that GBM contains more 3-hydroxyproline, neuraminic acids and mannose. These differences may contribute to the different immunogenic properties of the two basement membranes reported in the literature. Significant changes with age in the chemical composition were found, suggesting that the proportion of collagenous peptide moieties increases and that of noncollagenous peptide moieties decreases with age in both GBM and TBM. In addition, the hydroxylation grade of proline and lysine increases significantly with age reaching an adult level for GBM after 4-6 months of age and for TBM at late childhood. The age-related changes in basement membrane composition may influence functional properties of these extracellular renal structures. The chemical composition of GBM and/or TBM of the 4 patients showed some differences in comparison to control preparations from persons with ages approximating that of the patients.
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PMID:Variations in chemical composition of human glomerular and tubular basement membranes with age and disease. 732 36

The effect of diabetes on myocardial collagen metabolism was investigated in rats. Diabetes was induced by an i.v. injection of streptozotocin (60 mg/kg). The animals were killed after 3, 6, 18, or 26 wk of diabetes. Urinary glucose levels were measured by Tes-Tape. The myocardium was quickly removed and homogenized. Collagen was estimated by hydroxyproline content. Collagen synthesis was measured by 14C-proline incorporation. Myocardial collagen concentration and collagen synthesis was not altered in the diabetic rats. Collagen concentration did appear to increase in the 18- and 26-wk rats, but this was probably an age-related phenomenon. These results suggest that diabetes does not alter collagen metabolism in rats.
Diabetes 1980 Jul
PMID:Collagen metabolism in the myocardium from streptozotocin-diabetic rats. 738 Jan 16

The non-obese diabetic (NOD) mouse is a good model of insulin-dependent diabetes mellitus. Autoreactive T cells may play a fundamental role in disease initiation in this model, while disregulation of such cells may result from an abnormal thymic microenvironment. Diabetes is prevented in NOD mice by direct introduction of an E alpha d transgene (NOD-E) or a modified I-A beta chain of NOD origin (NOD-PRO or NOD-ASP). To investigate if disease pathology in NOD mice, protection from disease in transgenic NOD-E and NOD-PRO and partial protection from disease in NOD-ASP can be attributed to alterations in the thymic microenvironment, immunohistochemical and flow cytometric analysis of the thymi of these mouse strains was studied. Thymi from NOD and NOD-E mice showed a progressive increase in thymic B-cell percentage from 12 weeks of age. This was accompanied by a concomitant loss in thymic epithelial cells with the appearance of large epithelial-free areas mainly at the corticomedullary junction, which increased in size and number with age and contained the B-cell clusters. Such thymic B cells did not express CD5 and were absent in CBA, NOD-ASP and NOD-PRO mice as were the epithelial cell-free spaces, even at 5 months of age. Therefore the mechanisms of disease protection in the transgenic NOD-E and NOD-ASP/NOD-PRO mice may differ if these thymic abnormalities are related to disease.
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PMID:Studies on the thymus of non-obese diabetic (NOD) mice: effect of transgene expression. 752 87

L-fucose is a monosaccharide which is present in low concentrations in normal serum but is increased in diabetes, cancer, and inflammatory diseases. The contribution that abnormal L-fucose levels make to the progression of these disorders is unknown. In a previous study we showed that increased L-fucose concentration reduced proliferation and proteoglycan production by cultured cerebral microvessel endothelial cells. In the present study we show that exposing cerebral microvessel endothelial cells for 2 weeks to medium containing an increased concentration of L-fucose causes a significant decrease in collagen and to a lesser extent noncollagen protein production. The effect of L-fucose on collagen and noncollagen protein production is concentration-dependent: 1 mM L-fucose causes a significant decrease in collagen production but has no effect on noncollagen protein production; a 5 mM L-fucose concentration causes a maximum decrease in both collagen and noncollagen protein production. This defect is unrelated to the reduction in myo-inositol uptake caused by L-fucose and is not prevented by aminoguanidine. Collagen production can be improved by restoring L-fucose-conditioned cells to normal medium. Culturing cells for 2 weeks in medium containing 10 mM L-fucose resulted in a 50% decrease in collagen production, which was restored to 75% of control after cells were transferred to normal medium for 7 days. In contrast, noncollagen protein production was totally restored after 3 days in normal medium. Increasing levels of L-fucose in serum of rats also resulted in a decrease in collagen production. Collagenase digestible incorporation of L-[2,3,4,5-3H]proline into protein of the articular cartilage from rats fed a diet containing 20% L-fucose for 3 weeks was reduced by about 40% compared to rats fed a normal diet. The decrease in collagen production in L-fucose fed rats was less than the reduction that occurred in streptozotocin-induced diabetic rats. These data suggest that changes in L-fucose concentration itself may be a factor in the regulation of collagen production.
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PMID:L-fucose reduces collagen and noncollagen protein production in cultured cerebral microvessel endothelial cells. 759 46

Diabetes is known to cause impaired endothelium-dependent relaxation of blood vessels. The purpose of this study was to determine whether this endothelial dysfunction is a permanent defect or is reversible after acute arginine supplementation in vitro or by surgical intervention in vivo using syngeneic pancreatic islet transplantation. Lewis rats were injected with streptozotocin to induce diabetes and were studied either 8 or 12 weeks later. Another group received syngeneic islets via intraportal injection at 8 weeks of diabetes and were allowed to become euglycemic for 4 weeks before study. Thoracic aortic rings were tethered in isolated muscle baths, contracted with a submaximal concentration of norepinephrine, and challenged with either the endothelium-dependent vasodilator acetylcholine or the endothelium-independent vasodilator nitroglycerin. Relaxation to acetylcholine (but not nitroglycerin) was reduced in both 8- and 12-week diabetic rings compared with age-matched control rings. Preincubation of diabetic rings in vitro with L-arginine (but not D-arginine) restored relaxation to acetylcholine to normal to rings from 8-week but not 12-week diabetic animals. Plasma basic amino acids (arginine, lysine, and histidine) were reduced by diabetes, whereas other neutral or acidic amino acids were unchanged (phenylalanine, proline, and glutamate), reduced (serine, cysteine, threonine, tyrosine, tryptophan, and aspartate), or elevated (isoleucine, leucine, and valine). Islet transplantation restored to normal the changes in plasma amino acids. Elevation in blood glucose and total glycosylated hemoglobin in diabetic animals was normalized after islet transplantation. Furthermore, islet transplantation completely restored the defective endothelium-dependent relaxation to acetylcholine in diabetic rings.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1995 Sep
PMID:Syngeneic pancreatic islet transplantation reverses endothelial dysfunction in experimental diabetes. 765 36


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