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)

Pancreatic islets from adult rats were cultured in artificial capillary cultury units that were perfused with nutrient medium. In this in-vitro culture system, islets remain functional for at least 97 days. As determined by insulin radioimmunoassay of the culture medium, islets continue to secrete insulin. Furthermore, islets responded to high glucose concentration in the perifusion medium by increased insulin release throughout the duration of the culture period. A normal appearance of individual epitheloid islet cells and the presence of aldehyde-fuchsin-positive granules were observed in islets fixed in medium. As indicated by the prolonged maintenance of tissue-specific function, the present simple technique for organ culture of intact islets should be useful for providing new information on the long-term effects in vitro of various factors on islet function and a means for the preservation of islets for transplantation.
Diabetes 1977 Mar
PMID:Long-term survival of adult rat islets of langerhans in artificial capillary culture units. 32 75

In the present work, homogeneous isolated pancreatic islet-cells were transplanted to diabetic rats with the aim of verifying if the transplanted tissue could survive and reduce the plasma glucose concentration on the alloxan-induced diabetic receptors. For the isolation of the pancreatic islets, pancreas was incubated in collagenase solution for about 13 +/- 3 minutes, followed by centrifugation in Ficoll gradients. The islets, 3 000 to 5 000, were transplanted to alloxan diabetic recipients, in a territory, preferentially with portal-hepatic drainage (mesentery and spleen). Sixty per cent of the recipients exhibited a fall of the plasma glucose concentration, up to 70%, while in the control animals, the diabetes persisted. The islets were found in the recipients mesentery up to 10 days after transplantation, and all of them showed heavily granulated (aldehyde fuchsin positive) beta cells. After this time, islets were not found. These results indicate that islets can survive and attenuate diabetes in alloxan-treated rats, and that, probably, the number of islets transplanted as well as the receiving areas play an important role.
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PMID:Transplantation of islets of Langerhans in diabetic rats. 35 20

Isologous pancreatic islets were implanted into the portal vein of rats with streptozotocin-induced diabetes. At intervals of from one to 32 days after transplantation, the intrahepatic islet grafts were examined histologically and ultrastructurally, and their vascular supply was determined by later perfusion studies. Implanted islets were found widely dispersed throughout the liver in peripheral interlobular portal venules and surrounded by vacuolated liver cells containing large stores of glycogen. The endocrine cells were structurally normal in each interval examined. By the third day after transplantation the beta cells were depleted of secretory granules in aldehyde-fuchsin preparations. Regranulation returned by the 14th day and was associated with secretory organelle hypertrophy and hyperplasia. Islet cells were found outside the portal areas in direct apposition to hepatocytes forming distinct desmosomes by the first day. While hemoperfusion of the grafts occurred from the moment of implantation into the portal venule, a dual vascular supply derived from periportal arterial and venous sources developed by the 11th day after transplantation, establishing full vascularization of the grafts. Preliminary work is presented to show that an active ingrowth of nerves in the islet graft occurs in association with the process of vascularization.
Diabetes 1977 Mar
PMID:A morphologic study of intrahepatic portal-vein islet isografts. 40

Long term reversal of alloxan diabetes has been accomplished by intraperitoneal isotransplantation of enzymatically dispersed neonatal pancreas. In contrast, allotransplanted recipients showed only a transient recovery from the alloxan diabetes followed by a return to the diabetic state at the time of the homograft rejection. These data strongly suggest that the reversal of the diabetic state was a consequence of the transplanted islets. This conclusion is further supported by quantitative analysis of biopsied pancreases from successfully reversed recipients which reveals only 3% of the normal beta cell mass. By comparison, recovery of transplanted islets composed primarily of aldehyde fuchsin positive beta cells was routinely accomplished in these recipients. Utilization of the more specific unlabeled immunoperoxidase method has revealed that some of the transplanted islets are composed of cells positive for glucagon and somatostatin, as well as insulin. Other recovered transplanted islets (generally smaller in size) are composed primarily of one cell type or the other. The presence of insulin, glucagon, somatostatin, and delete pancreatic polypeptide positive cells in the islets of normal rat pancreas has been confirmed. In addition, cells reacting positively for these hormones have been observed in the alloxan diabetic rat pancreatic islets and in islets from reversed recipients. The time required for the disappearance of glycosuria and hyperglycemia (usually occurring from one to eleven weeks posttransplantation) appeared to be related to the amount and age of the donor islet tissue transplanted. Fetal islet tissue was more effective on a per milligram basis in reversing the diabetic state. In addition, while reversal was obtained by transplantation of as little as 5 mg of neonatal islet tissue, relatively large amounts (20 mg) were required before successfully reversed recipients responded normally to glucose tolerance test. By comparison, a similar reversal of diabetes with normal response to glucose load was attained by transplanting only 3 mg of fetal islet tissue. Quantitative morphological evidence of large increases in absolute islet mass, obtained in fetal transplants at the renal subcapsular site suggests that the superiority of fetal islet donor tissue may by in its high growth potential. No adverse effects of an in vitro organ culture period, prior to transplantation, were observed with regard to the ability of neonatal tissue to reverse the diabetic state or for fetal islet tissue to continue to survive at the renal subcapsular site. Likewise, no advantage in regard to amelioration of the homograft rejection response was observed in cultured islet tissue; allotransplants of which were rejected at the kidney site.
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PMID:Transplantation of islet tissue in the rat. 82 63

The incubation of dialyzed hemoglobin A with a number of phosphorylated glycolytic intermediates leads to the formation of covalent hemoglobin adducts that co-chromatograph with hemoglobin AIb. Phosphorylated hexoses (glucose-6-P, fructose-6-P, fructose-1,6-P2) and trioses (glyceraldelyde-3-P, dihydroxyacetone-P) containing a free aldehyde or ketone can glycosylate hemoglobin A nonenzymatically. From 7 to 12% of the hemoglobin can be modified after a 72-h incubation of an equimolar mixture of hemoglobin A and the phosphorylated intermediate. No significant formation of adduct was seen with a sugar alone (glucose, fructose) or glycolytic intermediate which had a blocked aldehyde (glucose-1-P, glucose-1,6-P2, UDP-glucose). The addition of an equimolar amount of 2,3-diphosphoglycerate reduced adduct formation. Evidently, the phosphate is needed to orient and stabilize the intermediate in the bisphosphoglycerate pocket of hemoglobin so that the addition reaction can proceed. All of the hemoglobin A adducts were indistinguishable form hemoglobin AIb by ion exchange chromatography and isoelectric focusing. The hemoglobin A-glucose-6-P adduct and hemoglobin AIb had a NaB3H4-reducible linkage in the beta chain. The concentration of hemoglobin AIb is elevated in patients with diabetes mellitus. This presumably reflects the increased concentrations of glycolytic intermediates (glucose-6-P, fructose-6-P, fructose-1,6-P2, dihydroxyacetone-P) which were found to be significantly elevated in the red cells of diabetic patients as compared with normal controls.
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PMID:Nonenzymatic glycosylation of hemoglobin. 85 10

A conspicious renal change associated with diabetes is the thickening of the basement membranes. This was generally considered diffuse and little attention was paid to its nodular character. In the present study of the nodules, their topo-optical reation, electron microscopic fine structure as well as their trypsin digestibility after periodic acid-sulphatation revealed their basement membrane character. The increased basophilia obtained by the aldehyde-bisulphite-toluidine blue reaction indicated an increased amount of sugar components, whereas the decreased double refraction and the red polarization colours a decrease of the micellary arrangement. The change is mostly observed in diabetics; the specific localization around the Henle loops may refer eventual hyperosmolar effects, whereas the nodular character points to the role of local factors.
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PMID:Nodular thickening of peritubular basement membranes in diabetic kidneys. 103 74

Mounting evidence indicates that aldose reductase catalyzed reduction of excess glucose to sorbitol initiates the onset of certain diabetic complications. However, the kidney contains a large amount of aldehyde reductase, another NADPH-dependent reductase. The study was designed to assess the importance of these reductases to sugar alcohol (polyol) production in the kidney. To study the ability to reduce aldoses to polyols, both aldose and aldehyde reductases were purified from rat kidneys. Incubation studies with purified enzymes clearly demonstrated the polyol formation by both enzymes. Galactose feeding induced polyol accumulation in both medulla and cortex of the rat kidney. Al 1576, a potent inhibitor of both enzymes, reduced this polyol accumulation in both cortex and medulla, while the selective inhibitors Ponalrestat or FK 366 resulted in greater inhibition in medulla than cortex. These results suggest that kidney polyols may be generated by both aldose and aldehyde reductases and that aldehyde reductase contributes to polyol production in the kidney cortex, the predominant site of diabetes-linked kidney lesions.
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PMID:Rat kidney aldose reductase and aldehyde reductase and polyol production in rat kidney. 144 70

Streptozotocin-induced, insulin-deficient diabetic adult rats were daily administrated either minocycline or a chemically-modified non-antimicrobial tetracycline (CMT) by oral gavage for a 3-week time period; untreated diabetic and non-diabetic rats served as controls. On day 21, all rats received an intravenous injection of 3H-proline followed by perfusion fixation with an aldehyde mixture at 20 minutes and 4 hours after isotope injection. The upper and lower mandibles of these rats were dissected and processed for quantitative electron microscopic autoradiography to study 3H-proline utilization by fibroblasts in the periodontal ligament (PDL) of molars. In the non-diabetic controls, at 20 min after 3H-proline injection, radioprecursor was incorporated by the Golgi-RER system of PDL fibroblasts. At the 4-h time period, most of the label was present over the collagen fibers around these cells. In contrast, PDL fibroblasts in the untreated diabetic rats showed marked abnormalities ultrastructurally and minimal uptake (20 min) and secretion (4 h) of labeled proline. At both time periods, in both minocycline- and CMT-treated diabetic rats, fibroblasts were structurally more normal and the radioprecursor was localized in the fibroblasts and the PDL matrix in a pattern similar to that seen in the control rats. These results suggest that the diabetes-induced structural abnormalities and suppression of synthesis and secretion of protein (presumably collagen and its precursor) by PDL fibroblasts can be restored to near-normal by administration of a tetracycline and that this effect is mediated by a non-antimicrobial property of this family of antibiotics.
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PMID:Tetracycline administration increases protein (presumably procollagen) synthesis and secretion in periodontal ligament fibroblasts of streptozotocin-induced diabetic rats. 146 May 49

Streptozotocin-induced, insulin-deficient diabetic rats were administrated either minocycline (MC) or a chemically modified non-antimicrobial tetracycline (CMT) by oral gavage for a 3-week period; untreated diabetic and nondiabetic rats served as controls. On day 21, all rats received an intravenous injection of 3H-proline followed by perfusion fixation with an aldehyde mixture at 20 minutes and 4 hours after isotope injection. The parietal bones of these rats were dissected and processed for quantitative electron microscopic autoradiography to study 3H-proline utilization by osteoblasts. At 20 minutes after 3H-proline injection, radioprecursor was incorporated by the Golgi-RER system of the osteoblasts in the periosteal surface of the control rats. At the 4-hour time period, most of the label was present over the collagen fibers of the osteoid. In contrast, the flattened bone-lining cells in the untreated diabetic rats showed minimal uptake (20 minutes) and secretion (4 hours) of labeled proline. In both MC and CMT-treated diabetic rats, the radioprecursor was localized in the osteoblasts and osteoid matrix in a pattern similar to that seen in the control rats at both 20 minutes and 4 hours after isotope injection. Labeling of the osteoid by the radioprecursor was greater as a result of CMT treatment than during minocycline treatment. These results suggest that the diabetes-induced suppression of synthesis and secretion of protein (presumably collagen and its precursor) by osteoblasts can be restored to near-normal levels by administration of tetracycline(s) and that this effect is mediated by a non-antimicrobial property of these antibiotics.
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PMID:Tetracycline administration increases collagen synthesis in osteoblasts of streptozotocin-induced diabetic rats: a quantitative autoradiographic study. 153 8

The substrate specificities of human aldose reductase and aldehyde reductase toward trioses, triose phosphates, and related three-carbon aldehydes and ketones were evaluated. Both enzymes are able to catalyze the NADPH-dependent reduction of all of the substrates used. Aldose reductase shows more discrimination among substrates than does aldehyde reductase and is generally the more efficient catalyst. The best substrate for aldose reductase is methylglyoxal (kcat = 142 min-1, kcat/Km = 1.8 x 10(7) M-1 min-1), a toxic 2-oxo-aldehyde that is produced nonenzymatically from triose phosphates and enzymatically from acetone/acetol metabolism. D- and L-glyceraldehyde and D- and L-lactaldehyde are also good substrates for aldose reductase. The aldose reductase-catalyzed reduction of methylglyoxal produces 95% acetol, 5% D-lactaldehyde. Further reduction of acetol produces only L-1,2-propanediol. Acetol and propanediol are two products that accumulate in uncontrolled diabetes. Both acetol and methylglyoxal were compared with glucose for their abilities to produce covalent modification of albumin. All three of these carbonyl compounds reacted with albumin to produce modified proteins with new absorption and emission bands that are spectrally similar. Both methylglyoxal and acetol are much more reactive than glucose. A new integrative model of diabetic complications is proposed that combines the aldose reductase/polyol pathway theory and the nonenzymatic glycation theory except that emphasis is placed both on methylglyoxal/acetol metabolism and on glucose metabolism.
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PMID:Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal, and diabetic complications. 153 26


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