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

Data are presented on the level of stable metabolites of prostacyclin I2-thromboxane A2 system in streptozotocin diabetes mellitus in rats. It is shown that simulation of streptozotocin diabetes mellitus leads to the reduction of 6-ketoprostaglandin F1 alpha content in the aortal wall tissue and blood plasma, and to a rise of thromboxane B2 level and the thromboxane B2/6-ketoprostaglandin F1 alpha ratio in the blood plasma. Inclusion of docosahexaenic and eicosapentaenic acid concentrate into the ration of animals with streptozotocin diabetes mellitus is conducive to normalization of the stable metabolite level in the prostacyclin I2-thromboxane A2 system.
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PMID:[Effects of docosahexaenoic and eicosapentaenoic acids on the state of metabolites of the prostacyclin I2--thromboxane A2 system in streptozotocin diabetes mellitus]. 138 92

This study tried to improve the number of viable islets isolated from a pancreas because a sufficient number cannot be obtained when the organ is preserved in the manner used for pancreas transplantation. The mechanism involved in the decrease in islet yield during preservation was studied to try to develop a better method for islet preparation. First, the integrity of the ductal system was compared between fresh and 6-hr simply preserved (in Hanks' balanced salt solution) rat pancreases. The ductal pressure after ductal injection of HBSS reached a plateau earlier and was significantly lower for the preserved pancreases (0.073 +/- 0.026 min, 410 +/- 17 mmHg, n = 5) than for the fresh ones (0.176 +/- 0.086 min, 561 +/- 103 mmHg, n = 7, P less than 0.05). Second, the extent of pancreatic distention was examined following ductal injection of barium gelatin solution. Solution leakage occurred earlier and distention was less in the preserved pancreas. In addition, the gelatin was found in the capillaries within some islets of the preserved pancreas. These results indicated that the preservation led to a rapid loss of integrity of the ductal system before collagenase injection. We therefore tested the efficacy of ductal collagenase injection at the time of harvesting: 15 ml of 1.0 mg/ml collagenase HBSS was intraductally injected and the pancreas was preserved at 4 degrees C for 2, 4, 6, and 24 hr. The isolation procedure was similar to that used for the fresh pancreas. The yield was significantly better than that of the simply preserved pancreas at 4 hr (241 +/- 22, n = 3, vs. 140 +/- 58, n = 3, P less than 0.05) and at 6 hr (171 +/- 58, n = 14, vs. 32 +/- 33, n = 6, P less than 0.01). These isolated islets were spherical-oval and their viability was confirmed by the ability to reverse STZ-induced diabetes in mice. These results indicated that the integrity of the ductal system, which is necessary for distention of the whole pancreas, was lost during preservation. To solve this problem, ductal collagenase injection should be done at the time of pancreas harvesting and then followed by simple preservation. This method is recommended to obtain viable islets from a preserved pancreas.
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PMID:Improvement in islet yield from a cold-preserved pancreas by pancreatic ductal collagenase distention at the time of harvesting. 184 29

To evaluate the potential of utilizing porcine islet tissue as an alternative to human islet tissue for transplantation, we developed a method for the isolation of large amounts of highly purified porcine islets, and assessed the in vitro and in vivo function of the isolated islets after 1, 4, and 7 days of culture. The pancreatic duct of the splenic lobe was cannulated and distended by injection of Hanks' balanced salt solution containing 1.5 mg/ml collagenase. The pancreas was then processed by a modification of the automated digestion-filtration method developed in this laboratory, and with purification accomplished by Euro-Ficoll gradients (dialyzed Ficoll in Eurocollins solution), consisting of two layers of 1.108 and 1.091 g/cm3 density, topped with a layer of HBSS. The postpurification yield was 5203 +/- 645 (mean +/- SEM) islets per gram of pancreas with a number of islet equivalents (IE) per gram pancreas (islet equivalence: 150-microns-sized islets) of 3551 +/- 305, and a volume of 6.27 +/- 1.7 mm3 islet tissue per gram of pancreas. The islet purity exceeded 90%. Overnight-cultured, perifused porcine islets released 53.1 +/- 8.2 pM insulin/200 IE at 3.3 mM glucose, and 114.9 +/- 25.4 pM insulin/200 IE at 16.7 mM glucose (P less than 0.001 vs. basal output). When theophylline was added, insulin secretion increased to 264.2 +/- 63.2 pM/200 IE (P less than 0.001 vs. basal secretion and P less than 0.005 vs. secretion at 16.7 mM glucose). After 4 days of culture, the islets still responded to secretagogues. The functional integrity of the isolated islets was confirmed by reversal of diabetes in aL3T4 antibody-treated C57B/B6 diabetic mice: normoglycemia was promptly restored by transplanting 1000 overnight- or 7-day-cultured (24 degrees C) islets under the kidney capsule. These results suggest that continued improvements of porcine islet isolation and culture could permit the use of porcine islets in immunoalteration and immunoisolation studies that may lead to eventual human transplantation.
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PMID:Automated large-scale isolation, in vitro function and xenotransplantation of porcine islets of Langerhans. 187 91

In this study we evaluated the impact of preoperative factors on the choice of intraocular tamponades (balanced salt solution and gas or silicone oil) and postsurgical visual function in cases of vitrectomy for proliferative diabetic retinopathy. We studied 150 consecutive vitrectomies for proliferative diabetic retinopathy, which were carried out from October 1987 to February 1989. The extent of central or peripheral traction and retinal detachment were found to have a major influence on the choice of intraocular tamponades. Different types of diabetes, renal failure, and the time interval since the last vitreous hemorrhage showed no influence on the choice of intraocular tamponades. Visual acuity was improved after vitrectomy in the group with silicone oil tamponade, as well as in the control group with BSS or gas tamponade. Patients receiving silicone oil had more advanced stages of proliferative diabetic retinopathy and therefore more complicated postsurgical courses. Silicone oil is more likely to be avoided in cases without retinal detachment, where the risk of further vitreous hemorrhage is felt to be low and in cases with complete panretinal photocoagulation. The present study supports the therapeutic value of complete panretinal photocoagulation for proliferative diabetic retinopathy--even in cases where the proliferative retinopathy progresses and a vitrectomy is needed. It is demonstrated that many patients requiring vitrectomy did not receive sufficient photocoagulation earlier.
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PMID:[Vitrectomy in proliferative diabetic retinopathy. Preoperative factors for surgical procedure and postoperative results]. 227 71

Seventy-nine mongrel dogs underwent total pancreatectomy. Fifteen dogs served as apancreatic controls and died 7.0 +/- 4.2 days later (mean +/- SD). The pancreases of 44 dogs (group 1) were intraductally distended by manual injection of Hanks' balanced salt solution (HBSS). Thereafter each organ was mechanically disrupted and subjected to collagenase digestion as described by Mirkovitch et al. The pancreases of 20 dogs (group 2) were intraductally distended and subsequently perfused with collagenase by a roller pump. The organs were then mechanically disrupted and filtered through screens as described by Horaguchi et al. The resulting tissue suspensions were injected into the spleens of the dogs as autotransplants in both groups, by direct punction of the splenic capsule in group 1 and by retrograde infusion via a splenic vein tributary in group 2. The functional outcome was better in group 2 than in group 1, as assessed by the number of animals that became normoglycemic after transplantation [15/20 (75%) vs. 13/44 (30%); P = .0025]. The degree of islet purification, as measured by an increase in the tissue insulin/amylase ratio, was higher in group 2, and in both groups it was higher in normoglycemic than in hyperglycemic animals. The percent engraftment [i.e., amount of insulin recovered from spleen as percent of tissue transplanted (mean, 15.4% in group 1 and 14.5% in group 2) or as percent of original pancreas (mean, 4.9% in group 1 and 4.4% in group 2)] was low in both groups but again was higher in normoglycemic than in hyperglycemic animals within each group. In conclusion, both the degree of engraftment and purification and the route of implantation influenced the functional outcome after dispersed pancreatic islet autotransplantation to the spleen of totally pancreatectomized dogs, with purified tissue injected retrogradely functioning better than unpurified tissue injected directly.
Diabetes 1986 Oct
PMID:Comparison of two methods of islet preparation and transplantation in dogs. 242 88

Insulin and branched-chain amino acids are known to stimulate protein synthesis in skeletal muscle. Extracts prepared from rat diaphragms after incubation in balanced salt solution and glucose alone yielded heat- and acid-stable, TCA-precipitable, nondialyzable factor(s) that inhibit protein synthesis when added to rabbit reticulocyte lysates. Polyribosomal profiles of inhibited lysates were consistent with a defect in peptide-chain initiation. Addition of insulin and amino acids to the diaphragm incubation media partially removed the inhibition seen with the muscle extract and was accompanied by an increase in polysomes and decreased subunits. Similarly, extracts prepared from rat hindlimb muscle 48 h after induction of diabetes were much more inhibitory in rabbit reticulocyte lysates than extracts from control rats. Polyribosomal profiles were consistent with defective peptide-chain initiation. Trypsin treatment before assay abolished the inhibitory activity of muscle extracts from diabetic rats. Because translation-inhibiting peptide(s) appear to be under metabolic and/or hormonal control, their possible role in muscle protein homeostasis warrants further study.
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PMID:Muscle protein synthesis: regulation of a translational inhibitor. 637 11

The free amino acid content of diaphragm muscles of control and diabetic rats was studied 5 days after the injection of streptozotocin. Muscles were prepared for analysis either immediately after sacrifice or following incubation in balanced salt solution containing 5.5 mM glucose, with or without an electron acceptor, 0.02 mM methylene blue. Diaphragms of diabetic rats contained significantly more free taurine, glutamate, and branched chain amino acids than the controls at sacrifice, and significantly less glutamine, serine, asparagine, lysine, arginine, histidine, threonine, citrulline, and carnosine. Alanine decreased in plasma of diabetic rats but not in diaphragms before incubation. Hemidiaphragms of diabetic rats produced less alanine and more glutamate during incubation than controls. After incubation they contained less than half as much alanine and glutamine and twice as much glutamate than the controls, having released approximately 40% less alanine and 25% more glutamate into the medium than the controls. Glutamine release was not significantly different between the two groups. Methylene blue increased the free alanine content in the tissue water as well as alanine release by control and by diabetic muscles; the glutamate content of muscles decreased concomitantly. The effects of methylene blue were greater in the diabetic group. Branched chain amino acid release by diabetic muscles decreased during incubation with methylene blue. Muscles of diabetic rats contained more alpha-ketoglutarate than the controls after incubation with or without methylene blue. Methylene blue increased the alpha-ketoglutarate content of muscles and its release into the medium, the effect being greater in diabetics than in controls. Hemidiaphragms from diabetic rats released less pyruvate during incubation than controls, while lactate release by the two groups was not significantly different. Incubation with methylene blue caused a marked increase in pyruvate release by diabetic muscles, and a lesser stimulation in controls; lactate release increased in both groups. After incubation the lactate/pyruvate ratio in muscles was lower in the methylene blue treated group. The in vitro effect of 0.02 mM phenazine methosulfate on alanine production was similar to that of methylene blue. The data is compatible with the hypothesis that the NADH/NAD ratio may exert a restraining effect on alanine production and release by muscle. The progressive increase in this ratio may play a role in the eventual deceleration of gluconeogenesis during a prolonged fast and may restrain this process in uncompensated diabetes.
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PMID:The effect of diabetes and the redox potential on amino acid content and release by isolated rat hemidiaphragms. 738 25

Clinical pancreatic islet transplantation requires cold storage of islets for some hours. The best solution for cold storage will be that which maintains islet viability for the longest time. We have examined the viability of rat and human islet after storage at 4 degrees C for up to 6 days in Hanks' balanced salt solution, University of Wisconsin solution (UW), and 2 modified versions of this last solution, Sumimoto D (SD) and histidine-lactobionate (HL). The integrity of cold-stored rat and human islets of Langerhans has been examined using supravital stains and electron microscopy. In addition, the viability of cold-stored rat islets was tested by intraportal transplantation into syngeneic streptozotocin-induced diabetic recipients. The in vitro studies showed good preservation of islets stored in UW, SD, and HL for up to 72 hr. In comparison, storage for periods as short as 24 hr in HBSS markedly reduced islet integrity. The transplantation studies showed that rat islets cold stored in HBSS solution for 24 hr were not able to reverse experimental diabetes, whereas those stored in the other 3 solutions for 24 hr successfully reversed diabetes within 1 week of transplantation. After 48-hr cold storage, only islets preserved in HL solution were uniformly capable of producing functioning islet grafts. None of the tested solutions was able to maintain islet viability sufficiently to allow successful transplantation after more than 48 hr of cold storage. These experiments demonstrate that good islet viability is maintained for up to 24 hr of storage in UW, SD, and HL, and even after 48-hr cold storage in HL solution, whereas preservation in HBSS solution was deleterious to islet viability within 24 hr.
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PMID:A comparison of four solutions for cold storage of pancreatic islets. 827 97

Addition of 10% albumin to the digestion medium has been suggested to enhance yield and integrity of harvested islets by inhibition of proteolytic activities and to improve endocrine function early after transplantation. The aim of this study was to evaluate in vivo by means of intravital fluorescence microscopy whether this rapid reversal of hyperglycemia after transplantation is due to improved graft vascularization. Pancreatic islets were isolated from Syrian golden hamsters by collagenase digestion using either solely Hank's balanced salt solution (HBSS) or HBSS supplemented with 10% human serum albumin. Islets were then transplanted into the dorsal skinfold chamber of syngeneic animals (control: N = 8 animals, n = 50 islets; albumin: N = 7, n = 41). The grafts' microvasculature was analysed on days 6, 10, and 14 after transplantation. Immunohistochemical staining for insulin was performed at the end of the microscopic observation period. Islet isolation with albumin supplementation did not increase islet yield. However, photomicroscopic analysis suggested a beneficial effect on the isolation process with improved islet integrity and prevention of outer margin irregularities, in particular in large islets. Analysis of revascularization 6 days after transplantation revealed in the control group a functional capillary density (FCD) of 477 +/- 47 cm-1. On day 10 FCD increased to 680 +/- 42 cm-1 with no further changes on day 14, indicating complete revascularization. Islets in the albumin group demonstrated a comparable FCD of 598 +/- 49 cm-1 on day 10 and complete revascularization on day 14 (655 +/- 45 cm-1). The angio-architecture of the islets was found similar in both groups, presenting with a glomerulum-like capillary network, comparable to that of pancreatic islets in situ. We conclude that the addition of 10% serum albumin to the collagenase digestion medium improves the preservation of the structural integrity of isolated pancreatic islets, however, does not influence the process of graft vascularization. Thus, improved early graft function may rather be due to superior preservation of islet cell integrity and function.
Exp Clin Endocrinol Diabetes 1997
PMID:Improved islet isolation by 10% albumin does not influence graft angiogenesis and vascularization. 922 11

To determine the potential value of measuring adenylylcyclase activity as a pre-transplant functional marker of pancreatic islet cell quality, a production rate of adenosine 3':5'-monophosphate was measured with a fluorometric assay in rat islet cells before transplantation. Islets were stored for different periods of time (0 to 96 hours) and in different preservation solutions. The adenylylcyclase activities of islets stored in University of Wisconsin (UW) solution for 3 hours after isolation were significantly higher than those stored in Hanks' balanced salt solution. Similarly, the adenylylcyclase activities of islets stored for more than 24 hours in UW solution decreased significantly with prolonged storage time. Preoperative adenylylcyclase activity was compared with post-transplant islet function in a rat model of diabetes. Transplant success was evaluated by measuring blood glucose level and body weight. Although all transplants were ultimately successful in this study, the rate at which they achieved euglycemia varied, and this is the property that correlated with pre-transplant basal or forskolin-stimulated adenylylcyclase activity. Additional studies showed that it was feasible to measure adenylylcyclase activity in human islet cells. We conclude that preoperative measurement of basal and stimulated adenylylcyclase activity may provide a useful clinical marker for assessing islet cell quality and differences in preservation media and may predict transplant success. Based on these data, additional studies evaluating the feasibility of using adenylylcyclase activity as a research and clinical marker of islet cell viability are warranted.
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PMID:Preoperative assessment of adenylylcyclase activity as a functional marker of islet cell quality after transplantation in rats. 1021 70


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