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

Preincubation of collagenase-isolated rat islets for 150 min with 100 U/ml purified human interleukin 1 (IL-1) altered their ability to secrete insulin. Whereas basal release rates with 4 mM glucose were comparable in control and IL-1-treated islets, both the first and second phases of release in response to 20 mM glucose were significantly reduced from IL-1-treated tissue. IL-1 pretreatment also impaired the secretory response to the combination of 100 nM cholecystokinin plus 7 mM glucose. However, the secretory response to 10 mM alpha-ketoisocaproate was comparable in control and IL-1-pretreated islets. Reducing the IL-1 exposure time to 60 min was accompanied by an augmented first phase of release to 20 mM glucose. Second phase secretion was diminished. The use of glucose measured after the perifusion was similar in control and IL-1-treated islets. Similar to other compounds that adversely impact on beta-cell viability, the inhibitory effect of IL-1 on release may presage a cytotoxic action of monokine.
Diabetes 1986 Oct
PMID:Interleukin 1 inhibits insulin secretion from isolated perifused rat islets. 353 Aug 42

We examined the ability of fibronectin, an extracellular glycoprotein that interacts with cell surfaces and matrix components, to bind to glomerular basement membrane and the effect of diabetes on this binding. 125I-labeled fibronectin binding to rat glomerular basement membrane (GBM) was dose dependent, related to time and amount of basement membrane, and inhibited by unlabeled fibronectin but not by unrelated proteins. Binding was reduced approximately 60% when GBM was pretreated with collagenase and approximately 24% when pretreated with chondroitinase plus heparinase. Treatment with NaCl had little effect on binding, whereas reduction with beta-mercaptoethanol removed approximately 25% of the bound 125I-fibronectin. Binding to samples prepared from rats with streptozocin-induced diabetes was significantly increased compared with that observed with control preparations at all concentrations of fibronectin and of basement membrane tested. The findings provide direct evidence that fibronectin binds to GBM and that this binding, which represents a biologic function of the protein, is enhanced in diabetes.
Diabetes 1987 Jun
PMID:Fibronectin binding to glomerular basement membrane is altered in diabetes. 356 74

Specific radioimmunoassays for the 7-S domain of type IV collagen and the fragment P1 of laminin were used to quantify these basement membrane proteins in human kidney cortex at different ages and in some patients with diabetes mellitus. The antigens were solubilized by treating the tissue samples with the proteolytic enzymes collagenase, trypsin and pepsin. Total collagen content (as indicated by hydroxyproline concentration) increased with age, and the proportion of the collagen that could be solubilized by any enzyme treatment decreased. The type IV collagen concentration increased significantly with age, whereas the laminin concentration tended to decrease. In the one case of a type I diabetic the amounts of both antigens exceeded those in the age matched controls. In four type II diabetics the results were comparable with those for other aged cases. The distribution of the proteins was studied using the peroxidase-antiperoxidase method. The staining intensity and thickness of both antigens increased with age in the mesangium and Bowmans capsules, the change in type IV collagen staining being more evident. In diabetic patients these changes were more pronounced and other basement membranes appeared thicker in the stainings. These results indicate that basement membrane material accumulates in the kidney cortex during aging and that an alteration takes place in the composition of the basement membranes, the proportion of type IV collagen increasing and that of laminin decreasing.
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PMID:Effect of age and diabetes on type IV collagen and laminin in human kidney cortex. 378 96

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

Long-term insulin secretion was investigated in seven biohybrid capillary devices seeded with canine islets. Approximately 50,000 islets could be isolated from a single canine pancreas using collagenase digestion in conjunction with the recently described Velcro technique. Devices were perfused with tissue culture medium 199 containing 300 mg/dl glucose. Insulin secretion fell during the first 1-2 days of culture from approximately 18 to 6 U/day. After 3-4 wk of perfusion, however, there was a gradual rise in insulin output that reached greater than 15 U/day after 7 wk. Insulin output eventually stabilized at 18-20 U/day. Two of these devices were studied for 80 and 86 days, respectively, and continued to secrete these same amounts of insulin. Glucose-induced insulin release was studied after 1 and 4 wk of culture and was well preserved.
Diabetes 1985 Sep
PMID:Biohybrid artificial pancreas. Long-term insulin secretion by devices seeded with canine islets. 392 20

The present study evaluates the development and function of human fetal B-cells in vitro with a view to using such cells in future attempts for transplantation of human fetal pancreas to diabetic patients. A method previously described in our laboratory for preparing islets in vitro from the fetal rat pancreas has been applied and modified for use with human fetal pancreas. Pancreatic glands of different gestational ages were obtained from 37 consecutive prostaglandin-induced abortions. After a mild collagenase treatment, the partially disintegrated tissue was maintained in culture for 7 days in tissue culture medium RPMI 1640 plus 20% fetal calf serum to permit cell attachment and out-growth of endocrine cells. In 17 of the 37 consecutively cultured fetal pancreatic glands, islet-like cell clusters were formed. The 20 remaining glands were lost because of either bacterial contamination or lack of viability already before dissection had occurred. Sections of the newly formed cell clusters revealed well-preserved pancreatic cells showing frequent mitotic figures. The tissue exhibited a high rate of (pro)insulin biosynthesis and a modest insulin response to secretory stimuli, suggesting that the mechanism of glucose regulation by the fetal B-cells is not yet fully developed. Electron micrographs showed a large number of granule-containing cells, some of which were identified as B-cells. In nine cases, harvested cell clusters were implanted beneath the kidney capsule of nude mice. When these animals were killed after 2 mo, seven mice showed a considerable growth of the grafts with numerous islet-like structures containing insulin- and glucagon-positive cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Nov
PMID:Tissue culture of human fetal pancreas. Development and function of B-cells in vitro and transplantation of explants to nude mice. 393 Mar 24

The nature of type IV collagen antigens in the serum of streptozotocin diabetic rats was studied using radioimmunoassays for the N-terminal (7S-collagen) and C-terminal domain of type IV collagen. Type IV collagen antigen crossreacting with antibodies to the C-terminal domain was elevated from 32.0 +/- 5.36 ng/ml (n = 10) in serum of normal rats to 94.9 +/- 24.5 ng/ml (n = 10, P less than 0.0001) in serum of streptozotocin diabetic rats and could be normalized to 40.1 +/- 8.30 ng/ml (n = 18) by insulin treatment. Molecular sieve chromatography of serum demonstrated a high molecular weight fraction containing the C-terminal and N-terminal domains and smaller material containing only the N-terminal domain. Degradation of the high molecular weight material by collagenase indicates that it consists of intact collagen type IV. Its relative proportion increased from 42% to 54% 4 weeks after diabetes induction. Together with unaltered clearance rates of 7S collagen in normal and diabetic rats, the data suggest that the increase of collagen type IV antigens in diabetic states reflects increased synthesis of collagen type IV.
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PMID:Type IV collagen antigens in serum of diabetic rats: a marker for basement membrane collagen biosynthesis. 409 61

Pancreatic islets of neonatal were dissociated by collagenase and cultured for 3 days in the presence of Cytodex beads to allow attachment of the cells to these microcarriers. The bead-attached cells were packed in columns and superfused with a low bicarbonate medium using the same method that we had originally developed for dissociated anterior pituitary cells of the rat. The secretion of insulin, somatostatin, and glucagon by the cells was monitored by radioimmunoassays. The cells in the superfusion system responded as expected from experiments with islet and monolayer cultures of rat pancreas in vitro and in vivo. Increasing glucose concentrations in the superfusion medium increased the release of insulin and somatostatin (SS), whereas glucagon secretory rates remained constant or decreased. A dose-response curve was established between insulin release and D-glucose in which the ED50 of D-glucose for insulin was found between 1.5 and 2 mg/ml. The phosphodiesterase inhibitor, 3-isobutyl-methylxanthine (IBMX), significantly potentiated the insulin response to glucose. Various secretagogues such as IBMX, 8-bromo cyclic AMP, and L-arginine increased insulin, somatostatin, and glucagon secretory rates in an expected manner. The superfusion method offers the possibility to investigate the interactions of dissociated A-, B-, and D-cells and the dynamics of hormone release in short- and long-term in vitro experiments. The method is simple and avoids the problems of monolayer procedures, such as clustering of the cells and poor adherence of dissociated pancreatic islet cells to dishes.
Diabetes 1982 Mar
PMID:Superfusion of dissociated pancreatic islet cells attached to Cytodex beads. 613 17

A new method for the preparation of viable islet cells from the normal dog pancreas is described, based on the perfusion of the pancreatic duct with collagenase. Exposure of the acinar tissue to the highest concentrations of collagenase results in improved islet yield with decreased acinar contamination. After the selective digestion of the gland by ductal perfusion, mechanical dissociation liberates single cells and clumps. Analysis of the procedure by insulin yield and amylase attrition indicates a 57% B-cell recovery and a sixfold enrichment in B-cell concentration. The cells have been transplanted as autografts into dogs after pancreatectomy. In 5 of 7 transplanted dogs, normoglycemia was achieved postoperatively.
Diabetes 1981 May
PMID:Preparation of viable islet cells from dogs by a new method. 616 88

A modified collagenase digestion method is described for the isolation of large numbers of islets from the canine pancreas (approximately 3,500 islets/g). The islets isolated by this technique remained viable and released insulin in response to secretagogues after one week of maintenance in tissue culture. Islets isolated from a single donor pancreas were re-implanted into the spleen of the same animal made diabetic by subtotal pancreatectomy and two injections fo streptozotocin. Hyperglycemia was corrected in two dogs and decreased in a third dog followed for 30 days. The islet isolation method is described, therefore, provides a sufficiently large yield of viable islets from one donor pancreas to correct or improve diabetes in a recipient animal.
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PMID:A method for large-scale, high-yield isolation of canine pancreatic islets of Langerhans. 617 32


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