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)

Dimethyl sulfoxide (DMSO, 7.3 g/kg) administered to mice prior to alloxan completely protected against the diabetogenic actions of 50 mg/kg alloxan. The same dose of DMSO provided a partial protection against 75 mg/kg alloxan. This protection against alloxan-induced diabetes is consistent with the scavenging of the hydroxyl radical by DMSO.
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PMID:The prevention of alloxan-induced diabetes in mice by dimethyl sulfoxide. 88 68

During the last few years new powerful diagnostic methods have been developed in the field of molecular and cell biology. It is now possible to work out the molecular pathology of many genetic diseases and to institute new techniques for the detection of carriers and neonatal diagnosis. However, it is in the field of polygenic diseases such as degenerative vascular disease, diabetes, cancer and other chronic diseases that molecular biology will play its most important part and perhaps change in the long term our clinical approach. There is considerable debate among geneticists on the safest strategy for obtaining and long term storing sufficient DNA from an individual for projects requiring large but unknown amounts of DNA. As little as 0.5 ml whole, blood samples (or white cells) which have been frozen with 10% DMSO or anticoagulants will provide sufficient DNA by direct extraction methods and also permit to establish lymphoblastoid cell lines providing an infinite source of DNA.
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PMID:[Reliability and power of genetic studies]. 149 41

Bepridil, a calcium antagonist with anti-anginal, anti-ischemic, and anti-arrhythmic properties was assessed for its ability to scavenge free radicals. Bepridil reduced the stable free radical 1,1-diphenyl-2-picrylhydrazil (DPPH) in the molar ratio 2:1 and, in this respect, was as active as the reference anti-oxidants hydroquinone and alpha-tocopherol. Allopurinol and SOD inhibited cytochrome c reduction in a hypoxanthine-xanthine oxidase superoxide generating system, whereas bepridil was ineffective. Deoxyribose degradation induced by the .OH radical was prevented by bepridil (IC50 = 0.050 mM). This ability to scavenge .OH was similar to that of dimethyl sulfoxide (DMSO) (IC50 = 0.056 mM) and more potent than that observed with mannitol and allopurinol (IC50 values of 0.74 mM and 0.92 mM, respectively). The powerful .OH scavenging activity of bepridil was confirmed in vivo on alloxan induced diabetes in mice. Bepridil exerted a marked protective effect at 0.150 mmol/kg whilst, ethanol and DMSO were active at the doses of 90 and 94 mmol/kg, respectively. These results demonstrate that bepridil is a potent .OH radical scavenger. This property may contribute to the therapeutic activity of this drug in myocardial ischaemia.
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PMID:Studies on the activity of bepridil as a scavenger of free radicals. 217 34

Techniques for freezing rat islets have been examined by the intensive use of the supravital stains fluorescein diacetate and ethidium bromide. By the use of a simple scoring system, the effect of the cooling rate, treatment with dimethyl sulfoxide (DMSO), rate of thawing, and postthaw culture were examined. These studies showed the most effective method to be a 24-h culture of islets, followed by partial incubation with 20% DMSO at 0 degrees C, followed by seeding at -8 degrees C in an alcohol bath. The islets were then cooled at a rate of -0.25 degrees C/min to -40 degrees C followed by quenching in liquid nitrogen at -196 degrees C. Rapid thawing at 37 degrees C was then followed by a 24-h culture. Islets from four Lewis rat donors were cryopreserved, counted, and transplanted intraportally into streptozocin-induced diabetic Lewis rats. Corresponding control transplants were performed with islets from four donors only cultured for 48 h. The results showed that reversal of hyperglycemia in severely diabetic rats was obtained at 5, 5, 6, 6, 6, or 8 days with cryopreserved islets from four donors, compared to reversal of diabetes at 1, 4, 5, 6, 7, and 12 days with islets from four donors subjected to culture alone. The new cryopreservation technique has several small modifications over previously described methods and results in a significant improvement in islet survival.
Diabetes 1989 Jan
PMID:Normalization of hyperglycemia in diabetic rats by intraportal transplantation of cryopreserved islets from four donors. 249 2

Reliable high-recovery human islet storage would facilitate tissue matching, organ sharing, and immune manipulation of donor islets and prospective diabetic recipients. Collagenase-isolated, Ficoll-purified pancreatic islets (median 21,000, 15% of total islet yield) from eight cadaver pancreases were cultured in vitro for 24 h, equilibrated in three steps with dimethyl sulfoxide (DMSO) to a 2-M concentration, supercooled, nucleated, and cooled at 0.25 degree C/min to -40 degrees C before storage at -196 degrees C for 44.25 +/- 8.75 days. Rewarming at 200 degrees C/min and removal of DMSO with 0.75 M sucrose preceded 48 h of culture and retesting. Recovery postthaw by microscope count on duplicate aliquots was 94.2 +/- 3.5% of prefreeze counts and by triplicate assay of extractable insulin was 90.0 +/- 22.3% on day 0 and 74.1 +/- 12.6% after a 48-h culture. Nonfrozen islets increased basal insulin secretion 7.7 +/- 2.8 times after stimulation with 300 mg/dl glucose in perifusion, whereas islets frozen-thawed and cultured 48 h increased 6.2 +/- 0.8 times (NS). Peak stimulated insulin release was 0.92 +/- 0.14 microU.islet-1.min-1 before storage and 0.73 +/- 0.14 microU.islet-1.min-1 (79% of control, NS) after freeze-thaw and a 48-h culture. Total insulin secretion (area under curve) was 66% of prefreeze values at 48 h. Immunocytochemical stains revealed preservation of islet morphology postthaw. Electron microscopy showed intact cellular and nuclear membranes and intracellular organelles. Frozen-thawed islets harvested 14 days after renal subcapsular xenografting in nude mice were revascularized and well granulated. Cryopreservation can achieve prolonged storage of large numbers of human islets with high recovery numerically and functionally, making this a feasible approach for future trials of human islet transplantation.
Diabetes 1989 Mar
PMID:Long-term cryogenic storage of purified adult human islets of Langerhans. 249 64

Dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, is known as an immunosuppressive agent and can reduce autoantibody levels in experimental autoimmune diseases. Because classic diabetogens damage the DNA and membrane of the beta-cell by the generation of free radicals, the purpose of these investigations was to determine whether the intake of DMSO or its derivatives methylsulfonylmethane (MSM) and dimethylsulfide (DMS) could prevent the expression of autoimmune diabetes in the spontaneously diabetic NOD mouse. DMSO (2.5%), MSM (2.5%), and DMS (0.25%) were added to the drinking water of female NOD mice immediately after weaning. Control animals were maintained on regular drinking water. The presence of overt diabetes was monitored from the age of 2 mo by weekly urinary glucose testing until the animals either became overtly glucosuric or were greater than 240 days of age. In contrast to what we expected, DMSO (2.5%) markedly increased the rate at which the animals expressed overt diabetes (P less than .0004, log-rank test). MSM had no effect, whereas DMS reduced the incidence and rate of diabetes onset. When DMSO (2.5%) was administered to male NOD mice and control strains of mice (BALB/c and ICR), the control group did not develop glucosuria or insipidus, whereas DMSO increased the incidence of diabetes in the male NOD mice from 21 to 79%. In contrast, when DMSO was fed to female NOD mice on a purified AIN-76 diet, diabetes onset was reduced to 36%. We conclude that DMSO accelerates the uptake of dietary diabetogens into the beta-cell of genetically susceptible animals (NOD mice). The protective effect of the purified diet in such animals may be due to a lack of putative diabetogens in purified diet, or alternatively, the diet itself contains factor(s) that protect the beta-cell from autoimmune attack and/or destruction.
Diabetes 1989 Feb
PMID:Dimethyl sulfoxide modulation of diabetes onset in NOD mice. 291 23

ICRF-187, (+)-1,2-bis(3,5-dioxopiperazine-1-yl)propane, has been shown to protect against alloxan diabetes (el-Hage et al., 1981). Since alloxan-induced pancreatic beta cell damage is thought to be mediated through the generation of highly reactive oxygen radicals by a metal catalyzed reaction involving both superoxide anion and hydrogen peroxide, in the present study the protective activity of ICRF-187 was compared with that of free radical scavengers, microsomal enzyme inhibitors and chelating agents. The free radical scavengers DMSO, vitamin E and WR2721 markedly reduced alloxan-induced hyperglycemia. ICRF-187 was found not to interact with superoxide anions, and there is no evidence to indicate that any of the known biological effects of ICRF-187 are mediated through free radical scavenging activity. SKF-525 and cimetidine, known inhibitors of drug metabolizing enzymes, also protected against the diabetogenic action of alloxan. Since it was found that ICRF-187 did not alter hexobarbital sleeping time, this compound must protect by a mechanism other than microsomal enzyme inhibition. Since the chelating agents EDTA and DETAPAC were found to protect against alloxan diabetes, ICRF-187 or its hydrolytic products, which are structurally similar to EDTA, could function as chelating agents. Transitional metals such as iron, zinc and copper were found to bind preferentially to a hydrolysis product of ICRF-187. Chelation of iron by ICRF-187 or its hydrolytic products could decrease in vivo formation of reactive oxygen radicals and provide a means for protecting against chronic anthracycline cardiotoxicity and alloxan diabetes.
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PMID:Mechanism of the protective activity of ICRF-187 against alloxan-induced diabetes in mice. 309 Jun 62

Cryopreservation of islets of Langerhans offers a number of important benefits for attempts to cure diabetes by transplantation. In the published literature, a variety of cooling rates, ranging from 0.25 to 75 degrees C/min, in conjunction with warming rates of 4-200 degrees C/min have been proposed to give optimal preservation of islets. In view of the general importance of rates of temperature change in determining survival and because of the possibility of modulating tissue immunogenicity by freezing and thawing, we have studied the interaction of cooling rate and warming rate for isolated rat islets that had been either fully or partially equilibrated with 2 M dimethyl sulfoxide (DMSO). Batches of islets were stored at -196 degrees C after cooling at 0.3, 3.0, 10, 30, 60, 150, or greater than 1000 degrees C/min and then warmed at either 10 or 50 degrees C/min. Survival was assessed by measuring the secretion of insulin during static incubation in alternating nonstimulatory and stimulatory media. Cooling rates extending over three orders of magnitude proved not to be a major determinant of survival when the islets were equilibrated with 2 M DMSO: greater than 50% survival was achieved at all cooling rates studied when the warming rate was at 50 degrees C/min. Peak survival (83%) was attained at a cooling rate of 0.3 degrees C/min, but only slightly lower recoveries were obtained at 60 and greater than 1000 degrees C/min. However, in islets only partially equilibrated with cryoprotectants, functional recovery was highly dependent on the cooling and warming rates, with peak survivals after slow cooling and rapid warming. Full permeation of the tissue with cryoprotectant offered maximal recovery of function.
Diabetes 1987 Jan
PMID:Interaction of cooling rate, warming rate, and extent of permeation of cryoprotectant in determining survival of isolated rat islets of Langerhans during cryopreservation. 309 10

Human fetal pancreatic glands were obtained from 12 consecutive prostaglandin-induced abortions. Explants cultured for 1 day were frozen at 0.3 degree C/min in a 1 M DMSO-containing medium and stored at -196 degrees C. After storage for 3-4 mo the frozen material was rapidly thawed and cultured 1 day before being tested for functional performance. There was a positive correlation between the pancreatic insulin content and the fetal crown-heel length. Seven of the twelve fetuses showed a marked insulin response to an acute glucose-theophylline challenge. In five of these pancreases there was a well-preserved morphology after thawing, whereas only one of the nonresponding preparations showed a satisfactory morphology. Pancreatic explants from three of four fetuses tested displayed evidences of an (pro)insulin biosynthesis. The combined results indicated that low-temperature storage of human fetal endocrine pancreas is compatible with specific functional survival.
Diabetes 1982 Mar
PMID:Preservation of morphology, insulin biosynthesis, and insulin release in cryopreserved human fetal pancreas. 675 40

Blood glucose concentrations were markedly elevated in CD-1 mice 48 hr after iv administration of alloxan (75 mg/kg). Treatment with three doses of ICRF-187 (96 to 345 mg/kg) given 60 min before and 4 and 8 hr after alloxan significantly attenuated the increase in blood glucose. Pretreatment with dimethyl sulfoxide (DMSO), a known free radical scavenger, at doses of 3.5 to 7.3 g/kg also protected against the alloxan diabetogenic action. When the lowest doses of ICRF-187 (96 mg/kg) and DMSO (3.5 g/kg) were combined, alloxan exerted no hyperglycemic effect. The protective effects of ICRF-187 and DMSO were confirmed morphologically. In alloxan-treated animals, beta cell granules were absent. In contrast, the degree of granulation showed only a mild to moderate reduction in those alloxan-treated animals given ICRF-187 alone, DMSO alone, or the combination of ICRF-187 and DMSO. These results suggest that ICRF-187 may alter the mechanism of free radical generation thought to be responsible for the production of alloxan diabetes.
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PMID:Reduction in the diabetogenic effect of alloxan in mice by treatment with the antineoplastic agent ICRF-187. 703 2


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