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

A large-scale isolation of islets is required for islet transplantation. We improved our conventional method, and could obtain about three times more islets than by the conventional methods. Pancreata of adult Wistar rats were inflated by injection of buffer with (A) or without 1.3 mg/ml collagenase (B). The rats were bled from the inferior vena cava and the aorta in (A) simultaneously with the inflation. They were further digested with collagenase and filtered through two different meshes (pore size: 1190 and 590 microns) (A1) or three different meshes (pore size: 1190, 590 120 microns) (A2) in order. Insulin released from islets isolated in this manner was determined by 1-h incubation with 3.3 and 16.7 mM glucose. Besides, 600 islets each were transplanted into the liver of streptozotocin-induced diabetic Wistar rats and their fasting plasma glucose was measured at weekly intervals. (1) With these methods more numerous islets were harvested by A1 (mean: 554) and A2 (mean: 746) than B (mean: 224). (2) Insulin released at both glucose concentrations was similar among islets obtained by A1, A2 and B. (3) The plasma glucose-lowering effect was similar among the islets obtained by these methods. (4) A more selected range of islet sizes was obtained by A2 than A1. These observations indicate that the present techniques (A1 and A2) are less time-consuming and simpler for a large-scale isolation of islets.
Diabetes Res Clin Pract 1989 Feb 15
PMID:Sophisticated mesh filtration technique of a large-scale isolation of islets and their function. 264 40

DNA synthesis, measured as 3H-thymidine incorporation, was estimated in islets obtained from BB rats before the onset of diabetes and compared with the replication rate of islets obtained from age-matched BB rats having never developed hyperglycaemia. Using a biopsy procedure, splenic pancreas was removed from both 65 and from 80 day old diabetes prone BB rats. After isolation by a modified collagenase method pancreatic islets were incubated with labeled thymidine. The animals submitted to biopsy were followed up until they reached an age of 200 days. The diabetes incidence of the BB rats biopsied at day 65 and at day 80 was comparable (35% and 31%). In both groups approximately 140 mg of splenic pancreas were necessary to isolate 70-90 islets, regardless whether the animals become diabetic or not. Using a retrospective experimental design, the thymidine incorporation into islets obtained from prediabetic (rats which developed hyperglycaemia) and from normoglycaemic BB rats were comparatively analysed. The DNA synthesis of pancreatic islets obtained from 65 day old prediabetic BB rats is not different from that measured in islets from normoglycaemic BB rats. A similar replicatory behaviour was also observed using islets from prediabetic and normoglycaemic 80 day old BB rats. From our results we seek to conclude that a prediabetic state is not related to a diminished replicatory activity of pancreatic islets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:3H-thymidine incorporation into islets obtained from prediabetic BB rats. 267 17

Skeletal abnormalities commonly reported in both human and experimental diabetes include impaired linear growth and osteopenia. In the present study we examined the effect of diabetes and insulin therapy on collagen, the major protein constituent of extracellular matrix. Insulin-deficient diabetes was induced in growing rats by injection of 90 mg/kg of streptozotocin. Articular cartilage and long bone (femur) were removed, and tissues incubated with [3H]-proline in vitro for 2 hours at 37 degrees C. Uptake of [3H]-proline into both collagen and noncollagen proteins was determined using purified bacterial collagenase. In cartilage, collagen production decreased to 46% of buffer-injected control animals within one week of induction of diabetes (p less than 0.01), and remained at this level for three weeks. A similar degree of suppression was found in long bone from untreated animals, in which collagen production decreased to 58% of control (p less than 0.01). Insulin administration at the onset of diabetes prevented the expected decrease in collagen production such that after one week of therapy, collagen production in bone and cartilage was 98% and 93% of control (p +/- 0.01 vs. untreated), respectively. When insulin therapy was delayed for one week after the induction of diabetes, collagen production in articular cartilage increased from 46% to 92% and 97% of control at the end of one and two weeks of therapy (p less than 0.01 vs. untreated), respectively. Noncollagen protein production in untreated rats decreased to 49% of control in long bone and to 72% of control in articular cartilage after one week (p less than 0.01), with correction to control levels in both tissues within one week of insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correction of altered collagen metabolism in diabetic animals with insulin therapy. 267 27

Although changes in collagen production probably play a major role in the connective tissue defects of diabetes, we do not know to what extent these changes are attributable to hormonal/metabolic versus nutritional alterations. To study collagen production as influenced separately by nutrition versus hormonal/metabolic factors, rats were given 50 mg/kg i.v. streptozocin (STZ) (mild weight-gaining diabetes) or 100 mg/kg STZ (severe weight-losing diabetes) and compared with nondiabetic food-restricted rats to match weight changes in diabetic animals. Articular cartilage was incubated with [3H]proline, and uptake of [3H]proline into both collagen and noncollagen proteins was determined with purified bacterial collagenase. Collagen decreased to 49% in mildly diabetic rats and 16% in severely diabetic rats, compared with control rats fed ad libitum and decreased to 85 and 73%, respectively, in food-restricted rats (both P less than .01 vs. diabetes). Diabetes induced a greater defect in collagen production than food restriction and a greater decrease in collagen than noncollagen protein production within each group, suggesting a specific effect on collagen. With comparable levels of metabolic severity (glucose, beta-hydroxybutyrate), diabetic animals that lost weight produced significantly less collagen than animals that gained weight, suggesting separate mechanisms. Quantitation of the impact of undernutrition on collagen production in diabetes demonstrated that approximately 31 to 32% of the defect was due to undernutrition, leaving approximately 68-69% of the defect due to the diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Jun
PMID:Nutritional and hormonal regulation of articular collagen production in diabetic animals. 272 23

The author describes his findings pertaining to spontaneous diabetes mellitus in BB rats and the method and results in juvenile alloxan diabetes in neonatal and adolescent Wistar rats of his own inbreeding F8-10. The author presents also the results of attempts to treat juvenile alloxan diabetes in rats by intrafamilial renal-subscapular allotransplants of 2-5 neonatal collagenase nondigested pancreases. Six of eleven BB females developed latent or manifest insulin dependent diabetes mellitus during the third to fourth month of life. An intraperitoneal injection of alloxan to 2-5-day-old rats causes, after two months of prediabetes, latent or manifest disease, in particular in males. In one-two-month adolescent fasting F6--10 inbred rats (Wistar strain) intravenous injection of 50 mg/kg alloxan causes diabetes mellitus with hyperglycaemia (20-60 mmol/l), glycosuria, polyuria, arrested growth, development of cataract and early death due to pulmonary or intestinal infection. The author tries to prevent these sequelae and complications by insulin therapy or intrafamilial allotransplantations of 2-5 neonatal, collagenase nondigested pancreases beneath the renal capsule, using two-three--week immunosuppression with Cyclosporin A combined with Azathioprine. The author proves permanent cure, histologically and functionally, by repeated allotransplantation which, however, due to the intense thymolymphatic immunological barrier in adolescent rats is less frequent than cure repeatedly achieved by the author in adult diabetic rats.
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PMID:[Spontaneous and experimental models of human juvenile diabetes mellitus]. 275 53

To obtain data concerning the pathology of diabetic arteries, aortas from 23 patients with diabetes mellitus [9 with insulin-dependent diabetes mellitus (IDDM) and 14 with non-insulin-dependent diabetes mellitus (NIDDM)] were collected at autopsy together with aortas from sex- and age-matched nondiabetic persons. A histomorphometric study was performed blindly on antifibronectin PAP-stained sections to determine the distribution of fibronectin-containing space in the vessels. In both IDDM and nonIDDM groups a statistically significant increase of approximately 45% was seen in the amount of stainable material in the tunica media. The increase was not influenced by the presence or absence of overlying plaque. No differences were seen between diabetic and nondiabetic vessels in the tunica intima. The content of extractable fibronectin in intima-media preparations was measured. The samples were extracted sequentially with buffered saline, a heparin-urea solution, and finally collagenase digestion. Fibronectin measured in these extracts showed that statistically significantly more of this glycoprotein was found in vessels from diabetic persons compared with nondiabetic persons, when comparing areas of the vessels without macroscopical visible plaque. However, only among IDDM patients increased amounts were apparent in plaque areas. These results indicate that diabetic patients develop structural alterations in the connective tissue of their arteries, consistent with a hypothesis of a diabetic macroangiopathy.
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PMID:Accumulation of fibronectin in aortas from diabetic patients. A quantitative immunohistochemical and biochemical study. 279 91

A combination of high-concentration collagenase digestion and density-gradient purification of canine pancreatic tissue made it possible to obtain relatively pure islets which could be quantified and the outcome of intrahepatic autotransplantation correlated with weight-corrected islet counts in the transplanted tissue. Of eleven dogs, seven achieved durable euglycaemia within 24 hours. All of these animals received islet doses of greater than 4,380 per kilogram of body weight. The remaining four animals became progressively hyperglycaemic necessitating sacrifice within one week; they all received islet doses of less than 4,380 per kilogram (p = 0.042). This model is therefore satisfactory for the investigation of preservation injury to islets and of allotransplantation because it identifies prospectively the transplants which ought to succeed, giving evidence for or against additional immune or ischaemic resistance to graft function.
Diabetes Res 1988 Nov
PMID:Weight-corrected islet counts are predictive of outcome in the canine intrahepatic islet autograft model. 285 30

In order to obtain an appropriate tissue model to study human diabetes we isolated islet cells from pancreata obtained from brain-dead, heart-beating kidney donor subjects by collagenase dispersion and tissue culture. The presence of viable islet cells was confirmed by both immunofluorescence staining and hormone release experiments. Insulin and somatostatin release were determined on culture day 3 or 4 when amylase measurements indicated an absence of functional exocrine cells. Glucose, alpha-ketoisocaproic acid, theophylline, glucagon, and tolbutamide each stimulated insulin release 2- to 3-fold and somatostatin release 1.5- to 2-fold. Epinephrine and somatostatin both inhibited glucose-stimulated insulin release. Successful subculture of islet cells was achieved after dispersion of primary cultures with dispase. Subcultured islet cells released insulin into the medium during a subsequent 8-day period and when challenged with glucose responded with a 1.6-fold increase in insulin output. Cells cultured on glass coverslips were used to detect, by indirect immunofluorescence, islet cell surface antibodies (ICSA) in the sera of patients with insulin-dependent diabetes mellitus. Of 15 sera from patients with newly diagnosed insulin-dependent diabetes mellitus 9 were ICSA positive, whereas all of 10 control sera were negative; in contrast, using rat insulinoma cells only 4 diabetic sera were positive, as well as 2 control sera. These findings demonstrate the functional viability of adult human islet cells in primary and secondary culture. Cultured human islet cells are a novel, sensitive, and specific system for detecting ICSA and for studying autoimmune effects, and provide a potential source of islet cells for transplantation.
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PMID:Adult human pancreatic islet cells in tissue culture: function and immunoreactivity. 286 82

The relationship between pancreatic hormone content and pattern of hormone release has not been completely elucidated because of heterogeneity in diabetes. Accordingly, this study was performed to establish the relationship, using spontaneously diabetic Chinese hamsters in the Asahikawa colony, a newly discovered experimental model resembling insulin-deficient diabetes in humans. As a result of investigations of insulin and glucagon responses to glucose or arginine in vivo and in vitro using isolated islets obtained by the collagenase procedure, a decreased insulin response and paradoxical glucagon response to glucose, and an excessive glucagon response to arginine were found in the diabetic animals. While the yield of isolated islets tended to decrease, a decreased pancreatic insulin content and increased pancreatic glucagon content were found as the diabetic state advanced. It may be suggested, therefore, that the relationship between pancreatic hormone content and pattern of hormone release in diabetic animals in the Asahikawa colony is based on the disruption of islets, disruption or dysfunction of B-cells and hyperplasia or hypertrophy of A-cells by some cause genetically determined.
Diabetes Res Clin Pract 1985 Aug
PMID:Insulin and glucagon response of the diabetic Chinese hamster in the Asahikawa colony. 287 8

Collagen production and collagenase activity were measured in dermal fibroblast cultures obtained from eight patients with diabetes with digital sclerosis and three normal controls. Total collagen synthesis in patients with diabetes was reduced in comparison with controls. DNA replication was also reduced in patients with diabetes. No differences in collagenase activity were noted. Our results suggest that, in contrast to systemic sclerosis, increased synthesis does not contribute to the collagen accumulation of diabetic digital sclerosis. Decreased degradation related to nonenzymatic glucosylation of collagen is a more likely mechanism.
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PMID:Collagen synthesis and collagenase activity in dermal fibroblasts from patients with diabetes and digital sclerosis. 298 79


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