Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Langerhans islets were isolated from the exocrine pancreata of Wistar rats by the improved collagenase-digestion method. The isolated islets were preserved in a tissue culture medium for seven days. Transplantation of these preserved islets into the portal vein of streptozotocin-induced diabetic rats resulted in a significant reduction of hyperglycemia, polyuria and glucosuria, and a restoration of weight gain. It was found that these effects could be maintained for 16 weeks. In order to normalize the K-values and plasma insulin levels, at least 600 islets had to be transplanted into each diabetic rat.
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PMID:Transplantation of preserved pancreatic islets into the portal vein of rats. 9 59

Lewis rats were treated with streptozotocin to induce hyperglycemia and glycosuria (400-600 mg/dl). Transplantation of approximately 1,000 dissociated islets obtained from collagenase-treated pancreases from 4 donors will promptly correct induced diabetes. Functional survival of islet allografts is related to genetic disparity between donor and recipient strains. In the closely matched Fisher-to-Lewis combination, islets functioned for a mean of 4.2+/-1 days while in the AgB-incompatible Wistar/Furth-to-Lewis combination, islets functioned for a mean of only 2.1+/-0.5 days. Treatment of recipients with antithymocyte globulin (ATG) for 3 days extended islet survival to a mean of 11.8 +/- 1.9 days in the Wistar/Furth-to-Lewis combination and to as long as 184+/-87.5 days in the Fischer-to-Lewis combination. ATG may have a role in trials of clinical islet transplants.
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PMID:Effect of antithymocyte globulin on islet of Langerhans transplantation. 10 12

Recovery from hyperglycemia was observed in streptozotocin diabetic mice that received subcutaneous, isogeneic transplants of either isolated islets or duct-ligated pancreas. Transplants of isolated islets obtained from collagenase-digested adult pancreas provided recovery from hyperglycemia, but the incidence of recovery depended on the amount of islet tissue initially transplanted. Hyperplastic, insulin-rich islets obtained from the pancreas of obese hyperglycemic mice (ob/ob) allowed recovery between 3 and 6 weeks, whereas an equivalent number of islets obtained from non-obese, normal donors gave only partial recovery after 8 weeks. Implantation of pancreatic endocrine tissue obtained from adult donors whose pancreatic ducts were ligated several weeks earlier, led to consistent recovery within 8 to 10 weeks. The content of immunoreactive insulin (IRI) extracted from transplants of mice recovering from hyperglycemia was 16 to 19% of that found in the normal mouse pancreas and was about 4 times greater than that remaining in the recepient's own pancreas. Transplants removed from hosts that did not recover contained a relatively small amount of IRI indicating that these transplants contained insufficient insulin stores to allow recovery form hyperglycemia.
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PMID:Subcutaneous, isogeneic transplantation of either duct-ligated pancreas or isolated islets in streptozotocin diabetic mice. 13 42

Forty-nine dogs were made diabetic by total pancreatectomy. Fifteen untreated pancreatectomized animals survived a mean (+/-S.E.) of 7.0 +/- 1.1 days with a mean (+/-S.E.) plasma glucose level of 402 +/- 26 mg/100 ml before death. The pancreata of 32 dogs were distended with cold (4 degrees ) Hanks' solution, minced, digested with collagenase (600 U/ml tissue) for 15-25 minutes, and autotransplanted either into the splenic artery (three dogs), directly into the splenic pulp (21 dogs), or into the portal vein (ten dogs). Tissue infusion into the splenic artery resulted in infarction and persistent hyperglycemia. Direct implantation into the splenic pulp of tissue digested for 15, 20 and 25 minutes resulted in permanent normoglycemia (fasting plasma glucose < 150 mg/100 ml) in 7 of 8, 7 of 7, and 6 of 6 dogs respectively. Glucose tolerance test mean (+/-S.E.) K values (% decline of plasma glucose concentration/minute) in these groups two weeks after transplantation were 1.20 +/- 0.20%, 1.60 +/- 0.25 and 0.70 0.08% respectively, indicating that 20 minutes digestion was best for intrasplenic transplantation. Tissue prepared in the optimal manner (20 minutes digestion) and embolized into the liver resulted in normoglycemia in three of eight dogs, and a mean (+/-S.E.) K value of 0.77 +/- 0.10%. Both dogs receiving tissue dispersed for 25 minutes into the portal vein remained hyperglycemic. In the dogs subjected to intraportal transplantation, portal pressure rose from a mean (+/-S.E.) of 6.5 +/- 0.6 cm H(2)O before to 21.9 +/- 2.2 cm H(2)O immediately after tissue embolization, but declined to 6.5 +/- 1.0 cm H(2)O by ten weeks in animals becoming normoglycemic. We conclude that in dogs direct implantation of pancreatic tissue into the splenic pulp is superior to embolization into the portal vein or splenic artery because the splenic circulation is not compromized, portal hypertension is obviated, and glucose metabolism is best controlled as judged by glucose tolerance test K values.
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PMID:Autotransplantation of pancreatic fragments to the portal vein and spleen of totally pancreatectomized dogs: a comparative evaluation. 33 53

The influence of hyperglycemia on the microvascular blood perfusion of pancreatic islet isografts of Syrian golden hamsters was analyzed by direct visualization of the islet's microvasculature by means of in vivo fluorescence microscopy. The experiments were performed using the hamster dorsal skinfold preparation, which allows for quantitative analysis of the microcirculation of islets grafted on the striated skin muscle. Islets were isolated from inbred hamsters by collagenase digestion and subsequently transplanted in normoglycemic (controls; n = 8) and hyperglycemic (65 mg/kg streptozotocin intravenously; n = 10) recipients. In both groups, revascularization of the islet grafts was completed on day 10 after transplantation. Quantitative analysis of capillary blood perfusion on days 6, 10, and 14 revealed no differences in functional capillary density and capillary red blood cell velocity of islets grafted into normoglycemic as compared to hyperglycemic animals. However, islet capillaries were significantly wider in hyperglycemic recipients (11.9 +/- 1.3 microns, P < 0.01) as compared to normoglycemic controls (8.9 +/- 0.4 microns). The increase of capillary diameters resulted in a significant rise (P < 0.01) of mean capillary blood perfusion from 1.76 +/- 0.39 nl/min in controls to 2.88 +/- 0.63 nl/min in hyperglycemic recipients, indicating an increase in microvascular blood perfusion due to hyperglycemia. From these results it is concluded that hyperglycemia is associated with higher capillary blood perfusion in revascularized islet isografts, similarly as known for pancreatic islets in situ.
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PMID:Influence of experimental hyperglycemia on microvascular blood perfusion of pancreatic islet isografts. 140 Oct 71

We examined the effect of chronic hyperglycemia on phosphoinositide hydrolysis and insulin secretion in isolated perifused rat islets. Rats were infused for 44 h with 40% dextrose in order to raise and maintain the plasma glucose concentration at 350 mg/dl. Control animals were infused with equiosmolar amounts of mannitol. In vivo insulin secretion and rats of glucose disposal were monitored throughout the study. At the end of the infusion, islets were collagenase isolated, and phosphoinositide (PI) hydrolysis (assessed by measuring the increment in [3H]inositol efflux as well as labeled inositol phosphates) and insulin output in response to a 20-mM glucose challenge were quantitated. Plasma insulin concentration and in vivo glucose disposal rates decreased significantly, by 47% and 35% respectively, after 6-8 h of hyperglycemia. In islets perifused immediately after isolation, prior in vivo hyperglycemia markedly altered the pattern of insulin output in response to 20-mM glucose challenge. Compared to mannitol infusion, 20 mM glucose stimulation resulted in an exaggerated first phase insulin secretory response (1121 +/- 88 vs. 467 +/- 75 pg/islets.min) and a blunted second phase insulin secretory response (392 +/- 90 vs. 1249 +/- 205 pg/islet.min). In islets prelabeled with myo-[2-3H]inositol for 2 h, PI hydrolysis, particularly [3H]inositol efflux in response to glucose stimulation was also reduced (0.28 +/- 0.03%/min) compared to that in mannitol-infused animals (0.53 +/- 0.08%/min). Two hours of preincubation in a low glucose medium (2.75 mM) were able to completely reverse the islet defect in both PI hydrolysis and insulin secretion. Our results demonstrate that chronic in vivo hyperglycemia impairs PI hydrolysis in perifused rat islets and suggest that this defect accounts in part for the abnormal pattern of glucose-induced insulin secretion.
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PMID:Chronic in vivo hyperglycemia impairs phosphoinositide hydrolysis and insulin release in isolated perifused rat islets. 215 64

Using a modification of the basic principles of pancreatic intraductal collagenase digestion and density gradient purification to isolate canine islets, in conjunction with simultaneous fluorogenic and dithizone islet staining, we quantified the yield, purity, and viability of the isolated islets. We then determined the combined influences of total and weight-corrected islet counts and implantation site on immediate and long-term functional outcome of purified canine islet autografts. Weight-corrected islet counts were 100% sensitive and specific in differentiating successful and unsuccessful islet autografts implanted to the liver (n = 10) and spleen (n = 10) of pancreatectomized dogs. The threshold number of islets required to achieve normoglycemia in the liver (4400 islets/kg) and spleen (4650 islets/kg) were nearly identical. Islet autografts failed to ameliorate hyperglycemia when implanted to the renal subcapsular space (n = 5) at counts of 4400 to 5500 islets/kg. The mean one- and three-month intravenous glucose tolerance test K-values of dogs with purified islet autografts to the liver (-1.43 +/- 0.27 and -1.69 +/- 0.27, respectively) and spleen (-1.78 +/- 0.36 and -1.64 +/- 0.3, respectively) were also similar. Time needed to achieve normoglycemia , however, was significantly (P less than 0.02) shorter for intrahepatic islets (1.0 +/- 0.0 days posttransplant) than intrasplenic islets (6.8 +/- 2.3 days posttransplant). The long-term durability of islet autograft function was not unlimited. Overall, thirteen canine islet autograft recipients have been followed for greater than or equal to 12 months posttransplant (range 12-18 months), seven canine islet autograft recipients (five intrahepatic and two intrasplenic) have had spontaneous recurrence of hyperglycemia at 2, 6, 11, 13, 14, 8, and 16 months, respectively. The phenomenon depended only on the number of islets implanted. The data underscore the significance of quantitatively defined islet preparations and the importance of islet number and implantation site on immediate and long-term functional outcome of canine islet autografts.
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PMID:Purified canine islet autografts. Functional outcome as influenced by islet number and implantation site. 216 62

In previous studies on streptozotocin-diabetic rats, transplantation of 1,000 (but not of 400) pancreatic islets to the renal subcapsular space was followed within 10 days by near-normalization of the impaired insulin secretion and the hyperglycemia. The long-term effects were now studied by measuring insulin and glucagon secretion 3 months after transplantation of 1,000 collagenase-isolated islets in streptozotocin (70 mg/kg) diabetic rats. At this time, diabetic control rats showed marked hyperglycemia and hyperglucagonemia, whereas the basal glucose and glucagon levels had normalized in the transplanted rats. Furthermore, insulin secretion in response to glucose or arginine stimulation and glucagon secretion following arginine stimulation were normal in all transplant rats, but absent in all diabetic controls. Morphologically the transplanted islets in the renal subcapsular space appeared normal on hematoxylin-eosin staining and immunostaining with antisera directed against insulin, glucagon, somatostatin and chromogranin A/B. Thus the islet transplants normalized basal hyperglycemia and hyperglucagonemia and restored insulin and glucagon secretion on a long-term basis.
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PMID:Islet transplantation to the renal subcapsular space in streptozotocin-diabetic rats. Long-term effects on insulin and glucagon secretion. 251 96

Human islets of Langerhans were isolated with the principles of collagenase perfusion via the pancreatic duct and gentle dissociation of tissue. The number of islets released was 161 x 10(3), distributed as 76 x 10(3) large (greater than 100-micron) and 85 x 10(3) small (less than 100-micron) islets. Recovery after Ficoll-gradient purification was 61% for the large islets and 42% for the small islets. The final islet volume was 240 microliter, with purity of 70-90% (large islets) and 20-40% (small islets). Perifusion with glucose elicited a biphasic release of insulin, with the response rising sixfold from basal secretion. Implantation of pure islets under the kidney capsule of normal or streptozocin-induced diabetic nude mice resulted in human C-peptide secretion and partial or complete reversal of hyperglycemia, confirmed by histological recovery. The data show that these methods provide large quantities of viable purified human islets.
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PMID:Viable purified islets of Langerhans from collagenase-perfused human pancreas. 253 89

The interhormonal relationship within the pancreatic islets have been studied by previous investigators, but the cellular interplay and the sequence of events in the islet cell's response to stimulators has remained unclear. In the present study, pancreatic islets were isolated by collagenase digestion from normal and streptozotocin-diabetic hamsters the latter being maintained with insulin treatment. The diabetic animals were used to provide A- and B-cell enriched islets. The islets from normal and diabetic hamsters were cultured in medium 199 plus 10% fetal calf serum with 0.8 or 5 mg/ml glucose. The cultures were maintained for up to seven days with medium changes every third day. At specified intervals, media were collected and assayed for insulin, glucagon and somatostatin. Our results showed the expected increased insulin secretion by the B-cells in response to high glucose. However, after two days of culture accumulative insulin secretory response was reduced and at the end of seven days was less than the insulin produced in low glucose medium. Glucagon secretion by the A-cells was similar for low and high glucose media for the entire culture period. Somatostatin secretion by D-cells was stimulated by high glucose but was attenuated after 2 days. No correlation could be found between the concentration of hormone in the media and a possible effect on a specific islet secretion. However, the fact that insulin secretion by islets cultured in high glucose was decreased after two days may indicate a refractoriness produced by persistent hyperglycemia. Islets isolated from diabetic animals secreted more glucagon and less insulin than control islets. Somatostatin secretion was the same in both groups. It was concluded that paracrine relationships were relatively insignificant in the regulation of islet secretion in a prolonged culture environment and persistent high glucose reduced the B-cell response to glucose stimulation.
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PMID:Insulin, glucagon and somatostatin secretion by cultured islets from normal and diabetic hamsters. 289 3


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