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

Isolated islets of Langerhans were obtained from sexually immature rats by means of collagenase. Interperitoneal isotransplantation of the islets to rats with alloxan diabetes caused an improvement of their condition, normoglycemia, and elevation of the immunoreactive insulin level, and prolonged survival of these rats, in the presence of coarse morphological changes in the endocrine part of the pancreas of the recipient (in 2--4 weeks). It is suggested that the insular cells of the islets of Langerhans isolated from the immature rats were viable.
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PMID:[Isolation of the islands of Langerhans and their transplantation under experimental conditions]. 9 54

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

Transplantation of adult rat pancreatic islet tissue as a free graft requires the separation of islet from exocrine tissue to avoid host injury or graft destruction by digestive enzymes. The poor yield from islet isolation techniques currently necessitates the use of multiple donors to ameliorate diabetes in a single recipient. DL-ethionine (DLE) is an agent selectively toxic to the exocrine pancreas. We examined the effect of DLE administration on pancreatic digestive enzyme content and islet mass in adult Lewis rats and the ability of such pancreatic tissue dispersed by collagenase digestion without specific islet isolation to ameliorate diabetes when transplanted to the portal vein of syngeneic rats with streptozotocin induced diabetes. Rats fed normal chow supplemented with 0.5% DLE for 14-20 days showed a logarithmic loss of pancreatic mass. Total pancreatic amylase content declined to 0.3 + 0.1 mg, less than 3% of control values (14.3 +/- 1.0 mg). Total insulin content in DLE treated rats was 87 +/- 8 microg, not significantly different from control rats (101 +/- 7 microg). Histological examination confirmed the selective atrophy of exocrine tissue in DLE treated rats. Fresh pancreatic tissue prepared from a single DLE treated donor ameliorated diabetes 75% of the time when transplanted to one or two recipients and 65% of the time when divided between three of four recipients. Tissue prepared from a single DLE treated donor and stored for 24-48 hours ameliorated diabetes 91% of the time when divided between one or two recipients. Only four of 31 diabetic rats transplanted with fresh pancreatic tissue from untreated adult donors became normoglycemic. Pretreatment of adult rats with DLE induces selective exocrine atrophy, permits dispersed pancreatic tissue from a single donor to ameliorate experimental diabetes in up to four recipients, and allows tissue to be preserved by culture for up to 48 hours without specific islet isolation.
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PMID:DL-ethionine treatment of adult pancreatic donors. Amelioration of diabetes in multiple recipients withe tissue from a single donor. 10 81

The effects of various experimental conditions during the isolation of monkey islets by the collagenase method on the insulinogenic response of the isolated islets to glucose have been studied and compared with rat islets isolated under similar conditions. The monkey islets gave a normal response for at least 120 min. The results are compared with available studies on primate islets.
Diabetes 1979 Sep
PMID:Studies on insulin secreted by isolated islets of the monkey, Macaca radiata radiata. 11 84

Intraperitoneal transplantation of collagenase-digested, isogeneic, neonatal rat pancreatic tissue successfully reversed streptozotocin-induced diabetes in 77% of recipients. The low serum immunoreactive insulin, hyperglycaemia, glycosuria and weight loss, characteristic of the diabetic animal, were corrected and the reduced activities of hepatic glucokinase and pyruvate kinase, and the low glycogen concentration of the liver of diabetic rats were restored to normal. Forty-three per cent of the successfully transplanted rats became normoglycaemic within 1 month of transplantation whereas 57% took from 1 to 6 months to achieve normoglycaemia and displayed a mild glucose intolerance when subjected to a glucose load. The rats which had not become normoglycaemic 6 months after transplantation showed some amelioration of the diabetic state, as shown by increased serum immunoreactive insulin and hepatic glycogen concentration and a slow weight gain compared with diabetic controls.
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PMID:Neonatal islet cell transplantation in the diabetic rat: effect on hepatic enzyme activity and glucose homeostasis. 14 94

PVG/C rats were made diabetic with streptozotocin and after 1 mth received a single intraperitoneal transplant of isogeneic collagenase digested pancreatic tissue. Renal changes have been studied in transplanted and control diabetic rats using light and electron microscopy and immunological techniques. Following transplantation, renal lesions did not increase in severity and progressive basement membrane thickening was prevented. Ultrastructurally many glomeruli showed a significant reduction in the mesangial matrix and the tubular and mesangial cell changes reverted to normal. Immunofluorescent studies demonstrated a similar reduction in the glomerular deposits of IgG. Possibilities for the treatment of diabetes mellitus in human patients are discussed.
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PMID:Neonatal islet cell transplantation in the diabetic rat: effect on the renal complications. 15 5

The inhibitory actions of somatostatin (100 ng./ml.) on insulin release, stimulated by high glucose (20 mM), and on glucagon release, stimulated by arginine (15 mM), were studied with two in vitro systems: the isolated perifused rat islets prepared by the collagenase procedure and the isolated perfused rat pancreas. Suppression of arginine-induced glucagon release by glucose (20 mM) and glyceraldehyde (5 mM) was also assessed in both systems. With the perfused pancreas, somatostatin caused 32 per cent inhibition of glucose-mediated insulin release and inhibited arginine-induced glucagon release by 72 per cent. In the same system, glucose and glyceraldehyde were similarly potent inhibitors of arginine-induced glucagon secretion. In contrast to the isolated perfused pancreas, there was no significant somatostation suppression of glucose-induced insulin release or arginine-induced glucagon release whether the inhibitor was present prior to or was added during stimulation by glucose or arginine. Furthermore, glucose was only minimally active and glyceraldehyde ineffective in inhibiting glucagon secretion due to arginine in the perifusion system. The most plausible explanation for the difference in the endocrine response of islet cells in the two types of widely used in vitro systems is that the alpha and beta cells have lost inhibitory receptors in the plasma membrane as a result of the collagenase isolation technic.
Diabetes 1975 Nov
PMID:Comparison of alpha- and beta-cell secretory responses in islets isolated with collagenase and in the isolated perfused pancreas of rats. 17 Nov 90

Standardization of a technic for isolating large numbers of pancreatic islets is described. This procedure employed collagenase digestion of rat pancreatic tissue in a cylindrical wire screen in order to separate isolated islets from undigested pancreas. From this basic protocol the following conditions were established: (1) the duration of the initial digestion period was found to be optimal at six minutes; (2) three subsequent digestions of one minute each effected maximum islet yield; (3) the optimal initial collagenase concentration was found to be 1,000 U. (Worthington)/ml.; and (4) proper reductions of collagenase concentrations during the three subsequent digestions were found to be 50 per cent of each preceding incubation period. This method, combined with Ficoll gradient separation, yielded a mean of 800 islets per two rat pancreases. The isolated islets appeared morphologically intact, contained 0.36 +/- 0.05 mug. protein/islet, and demonstrated a normal biphasic release of insulin in response to stimulative levels of D-glucose. The present method provides a means for obtaining a large mass of viable islet cell tissue in a short time.
Diabetes 1976 Aug
PMID:Standardization fo a digestion-filtration method for isolation of pancreatic islets. 18 6

Twelve pancreases from human infants one year old or less were analyzed for tissue insulin and amylase content before and after dispersal of pancreatic fragments by mincing and collagenase digestion. Tissue insulin and amylase content provide an index of pancreatic islet mass and exocrine digestive enzyme content, respectively. The results were compared with similar anaylses performed on juvenile and adult human pancreases before and after islet isolation and on intact and dispersed neonatal rat and adult rat pancreas. Infant human pancreas has an average tissue insulin concentration of 1,128 mug./gm. of tissue and a total insulin content of 1,718 mug/pancreas, as against values of 140 mug./gm. of tissue and 7,209 mug./pancreas for adult human pancreas. Average tissue amylase concentration is 0.24 mg./gm. of tissue in infant human pancreas and 3.0 mg./gm. of tissue in adult human pancreas. The insulin/amylase ratio in infant pancreas is 4,800, as against 46 in the adult pancreas. Neonatal rat pancreas, which can be dissociated and transplanted without separation of islet and exocrine components, has a similarly high tissue insulin and low tissue amylase content when compared with adult rat pancreases. Infant human pancreas has a total islet mass 24 per cent that of an adult human pancreas, and neonatal rat pancreas has a total islet mass 11 per cent of that of an adult rat pancreas. One neonatal rat pancreas prepared by minimal collagenase digestion can cure diabetes when transplanted via the portal vein to a rat. Following dispersal of infant human pancreas by collagenase digestion, the islet content and the insulin/amylase ratio of the recovered tissue equals or exceeds that which usually can be isolated from adult cadaver pancreases. Infant human pancreas is a rich source of islet tissue that is relatively uncontaminated by exocrine digestive enzymes. After dispersal, infant human pancreas may be ideal for transplantation to selected diabetic patients.
Diabetes 1976 Dec
PMID:Infant human pancreas. A potential source of islet tissue for transplantation. 18 47

In mongrel dogs, the horizontal part of the pancreas was infiltrated with collagenase, cut in pieces, incubated with collagenase, rinsed twice by centrifugation or sedimentation, and implanted into the spleen of the same animal. The operations were terminated by the removal of the rest of the pancreas. Of 26 operated dogs, one died because of a duodenal perforation, five developed severe hyperglycaemia without remission, and 20 were long-term normoglycaemic survivors followed for up to 10 weeks. These 20 animals became spontaneously normoglycaemic in the course of the first 10 postoperative days. Later, during glucose loading tests, the pattern of blood sugar values was the same in the transplanted animals as in those of a group of non-operated dogs, but the insulin release, although immediate, attained half the control values. The plasma insulin in the splenic vein was more than seven times higher than in the peripheral circulation. Splenectomies performed in seven animals were followed by severe hyperglycaemia and death. Light and electron microscopy demonstrated the presence of the intact endocrine and exocrine pancreatic tissues in the spleens of all animals investigated. It is concluded that laborious separations of endocrine from exocrine tissue are not mandatory for ulterior endocrine function, and that in an animal larger than rodents it is possible to obtain a diabetes-preventing function after the transplantation of only a part of the gland.
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PMID:Intrasplenic autotransplantation of canine pancreatic tissues. Maintenance of normoglycaemia after total pancreatectomy. 19 90


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