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

Pancreases from neonatal rats four to 16 days postpartum were grown in organ culture for from two to nine days. Approximately 10-20 explants, each measuring 1 mm.3 (1 mg.), were grown on a single Millipore filter placed at the gas-liquid interface of a medium consisting of 50 per cent horse serum and 50 per cent chick embryo extract. Following organ culture, an estimated 9-20 mg. of cultured islet tissue were dissociated with collagenase and isotransplanted into the peritoneal cavity of alloxan-diabetic recipients. In seven of eight recipients the diabetes was reversed between 11 and 53 days of posttransplantation. Animals receiving 12-16 mg. of cultured islet attained normoglycemia in 11-20 days; animals receiving 9-10 mg. of cultured islet tissue recovered between 45 and 53 days. These animals have remained symptom-free for over six months. Biopsies of grafts taken from the peritoneal cavity following reversal of diabetes contained well-vascularized islets compared primarily of heavily granulated beta cells. Quantitative analysis of host pancreases by the linear scanning method (biopsied at one to two weeks and four to five months following reversal of the diabetes) demonstrated that the total beta-cell mass was 3 per cent and the total insulin content was 6 per cent of the normal values. Little or no evidence of regeneration of host beta cells was observed. These studies show that a period of organ culture prior to isotransplantation does not impair the ability of islet tissue to reverse alloxan diabetes in the rat.
Diabetes 1976 Mar
PMID:Isotransplantation of organ-cultured neonatal pancreas: reversal of alloxan diabetes in the rat. 76 84

Accelerated periodontal tissue destruction in patients with labile insulin-dependent diabetes mellitus (DM) and localized juvenile periodontitis (LJP) has been suggested to be related to functional abnormalities of neutrophils. We have recently found that collagenase in gingival crevicular fluid (GCF) of adult periodontitis patients is primarily derived from neutrophils and that neutrophil collagenase activity is more sensitive to inhibition by tetracyclines than collagenase produced by fibroblasts. This study is to characterize the cellular sources, activation and inhibition of collagenase in GCF of DM patients and to compare it with collagenase in LJP GCF. We found differences which may have therapeutic implications. Specific doxycycline inhibition tests revealed that GCF collagenase in DM is derived from neutrophils, whereas the enzyme in LJP originates primarily from fibroblasts. Oxidant, sodium hypochlorite, activated efficiently GCF collagenase of DM but not LJP patients. In contrast, plasmin activated LJP GCF collagenase but not that of DM patients. In GCF of DM patients 50-60% of collagenase existed in an active form, whereas in LJP GCF, the enzyme was almost completely in a latent form. The results suggest that collagenase in GCF of periodontitis patients with labile DM is primarily derived from neutrophils and that tetracycline therapy may be an effective adjunct in treatment aimed at controlling the periodontal breakdown in these patients. On the other hand, in LJP the anti-collagenase property of tetracyclines may be less important for control of periodontal tissue destruction because of the tetracycline-resistance of fibroblast collagenase.
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PMID:Cellular source and tetracycline-inhibition of gingival crevicular fluid collagenase of patients with labile diabetes mellitus. 131 30

The expression of a novel regenerating (reg) gene has been reported previously in the regenerating islets of a surgical model of diabetes in rats. We exposed collagenase-isolated rat islets for three days to nutrient and non-nutrient growth factors in minimally supplemented RPMI medium (2.7 mmol/l glucose, 2% fetal calf serum), and investigated the relationship between reg gene expression and islet cell replication. RNA was prepared from half of the islets by homogenisation in guanidinium isothiocyanate followed by phenol/chloroform extraction. Northern/dot blot analyses were used to semi-quantify reg mRNA. Islet cell replication was estimated by culturing the remaining islets in radiolabelled thymidine to determine de novo DNA synthesis. Thymidine uptake was stimulated by the following factors: 11 mmol/l glucose (50% increase); 10% amino acids (126% increase); 10% fetal calf serum (39% increase); 100 ng/ml insulin (45% increase); 250 ng/ml growth hormone (65% increase); 1.5 nmol/l aldosterone (29% increase); 2 U/ml platelet derived growth factor (116% increase). The results are expressed as a percentage of the thymidine incorporated into control islets cultured in minimal RPMI (1118 +/- 100 (SD) cpm/microgram protein, n = 15). Increased islet cell replication was paralleled in each case by a clear rise in reg mRNA expression compared to controls. Furthermore, the rank order for reg gene expression was the same as that for thymidine uptake (r = 0.90). The present findings suggest a clear association between reg gene expression and islet cell replication in vitro, and are the first to demonstrate reg gene expression in response to individual growth factors.
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PMID:Expression of an islet regenerating (reg) gene in isolated rat islets: effects of nutrient and non-nutrient growth factors. 137 94

Type I diabetes is characterized by insulin insufficiency due to lack of functional beta cells. To replace injection therapy, schemes such as the Hybrid Artificial Pancreas (HAP) were developed. This consists of an acrylic housing enclosing a semipermeable hollow fiber membrane. Donor islets can be seeded in the annular space through a port in the housing, and thus are separated from the recipient's bloodstream or perfusate. Before scaling the HAP to human size, the dynamics of its insulin response to a perfusion glucose challenge must be better understood. In this study, the HAP's insulin response after a step increase in the lumenal glucose concentration was determined as a function of the radial thickness of the annular space (0.173-0.973 mm) and islet distribution at a flow rate of 1 ml/min. Devices containing a single, 65 mm long fiber were used. Rat islets were isolated using standard collagenase digestion techniques. In unseeded HAP perfusions, the washout time for glucose and insulin from the annular space was dependent on flow rate and radial thickness. Both solutes were removed in < 3 min from the smallest devices when perfused at 10 ml/min. Thus, solute transport within the HAP is very fast. In the seeded HAP perfusions, the devices were subjected to a step increase in the lumenal glucose concentration. Sequential samples of the HAP effluent were collected and assayed for glucose and insulin. The spatial distribution of the islets in the annular space was one of the most important factors in determining the HAP's insulin response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro perfusion of hybrid artificial pancreas devices at low flow rates. 145 99

Human islets were isolated by collagenase digestion and tissue culture from pancreata obtained from organ donor subjects and dispersed islet cells were prepared from hand-picked islets. Islet cell surface antibodies (ICSA), detected by indirect immunofluorescence on isolated islet cells, were present in sera from nine of 22 (41%) subjects with recent-onset insulin-dependent diabetes mellitus (IDDM) and three of 11 (27%) control subjects. Sera had been heat inactivated, adsorbed against a human B lymphoblastoid cell line (IM-9) and tested in the presence of 4% bovine serum albumin. However, with a double labelling technique, we were unable to show that ICSA were specific for beta cells. Of the nine ICSA-positive IDDM sera, three stained both beta and non-beta cells, three beta cells only and three non-beta cells only; the three ICSA-positive control sera stained both beta and non-beta cells. There was no apparent relationship between ICSA and standardised measurements of islet cell antibodies (ICA) and insulin autoantibodies (IAA). These results lead us to question whether, despite previous reports, ICSA are specific for beta cells or indeed for IDDM.
Diabetes Res Clin Pract 1992 Jul
PMID:Lack of specificity of islet cell surface antibodies (ICSA) in IDDM. 151 59

Collagen production has been shown to be decreased in costal cartilage from nondiabetic animals after incubation with diabetic rat serum. Since collagen was decreased to a similar degree in tissues from diabetic animals, we questioned whether altered collagen production in vivo could be related to altered production induced in vitro. Collagen and noncollagen protein production in articular cartilage from diabetic animals (production in vivo) was compared to protein production in dermal fibroblasts from non-diabetic rats exposed to serum from the same diabetic rats (production in vitro). Diabetes was induced by intravenous administration of 90 mg/kg of streptozotocin into male Sprague-Dawley rats. Cartilage was removed and incubated with [3H]-proline for 2 hours at 37 degrees C (in vivo), while fibroblasts were exposed to experimental serum from individual animals for 24 hours with addition of 5 microCi of [5-3H]-proline for the final 6 hours (in vitro). Collagen and noncollagen protein production were quantitated using purified bacterial collagenase. Collagen production in cartilage decreased to 46% (p less than .01) and noncollagen to 68% (p less than .05) of levels in control animals. Fibroblasts exposed to 2.5% diabetic serum decreased collagen and noncollagen protein production to levels of 30% (p less than .01) and 54% (p less than .05) of production in cells incubated in 2.5% normal rat serum. Correlation between defective collagen production in cartilage from individual rats and the effects of their own serum on collagen production in fibroblasts was significant (r = 0.84, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between decreased collagen production in diabetic animals and in cells exposed to diabetic serum: response to insulin. 160 33

Long-term survival of dog islet allografts implanted in diabetic pancreatectomized dogs was achieved by islet encapsulation inside cylindrical chambers fabricated from permselective acrylic membranes (nominal M(r) exclusion of 50,000-80,000). Dog islets were isolated from the pancreases of outbred mongrel dogs by collagenase digestion. Chambers containing mean +/- SE 316 +/- 63K islet equivalents (mean islet volume, 558 +/- 111 mm3, purity 90-95%) were peritoneally implanted into six totally pancreatectomized dogs. The dogs were monitored for glycemic control by fasting and postprandial blood glucose determinations, and responses to both intravenous glucose (intravenous glucose tolerance test 0.5 g/kg) and oral glucose (oral glucose tolerance test 1 g/kg). All of the dogs required appreciably lower dosages of exogenous insulin therapy for control of fasting blood glucose levels, with the mean daily insulin dose dropping from 38 +/- 7 to 5 +/- 1 U/day during the 1st wk. Three recipients required no insulin for greater than 82, greater than 68, and 51 days. Intravenous glucose tolerance test K values (decline in glucose levels, %/min) at 1 and 2 mo postimplantation were 2.7 +/- 0.4 and 2.0 +/- 0.5, respectively compared with 3.5 +/- 0.5 before pancreatectomy. The glucose values during oral glucose tolerance tests at 2 wk, although returning to less than 125 mg/dl (less than 7.0 mM) by 2 h, exceeded the normal range, with peak values of 174 to 202 mg/dl (9.7 to 11.3 mM). These preliminary results are encouraging, and represent an important step in determining the feasibility of using this type of diffusion-based hybrid artificial pancreas as treatment for diabetes mellitus in humans.
Diabetes 1992 Jul
PMID:Treatment of severely diabetic pancreatectomized dogs using a diffusion-based hybrid pancreas. 161 4

A simple method for the isolation of porcine islets of Langerhans is described. The technique, based on sequential collagenase digestion and density gradient separation through Percoll at unit gravity, produces islets which secrete insulin in response to glucose stimulation in static incubation, show bi-phasic release of insulin when perifused with 16 mM glucose, and can be maintained in culture for six weeks.
Diabetes Res 1991 May
PMID:Isolation of islets of Langerhans from the weanling pig. 166 60

Both insulin and glucocorticosteroid (GS) deficiency causes a reduction of amylase synthesis and changes in the dose-response curve of cholecystokinin (CCK) stimulated enzyme secretion in rats. Since we found a reduction of plasma insulin in adrenalectomized rats, we now tested the hypothesis that the regulation of amylase synthesis by insulin may be mediated by GS. Three groups of male rats were investigated: controls, streptozotocin induced diabetics, and diabetics treated with GS. Animals were sacrificed 10-14 days after injection of streptozotocin and isolated pancreatic acini prepared by collagenase digestion. Protein synthesis was measured on the translational level by incubation of acini with 35S-methionine followed by lysis of cells and separation of proteins by SDS-PAGE. In addition, protein synthesis was measured on the transcriptional level by isolation of mRNA from pancreatic acini and translation of proteins using the rabbit reticulocyte lysate system. The loss of insulin in diabetic rats was associated with a 70-90% decrease in amylase synthesis and increases of synthesis of various proteases. This was due to a specific decrease in mRNA coding for amylase and increase in mRNA coding for proteases. Furthermore, the known rightward shift of the dose response curves of CCK stimulated amylase secretion was seen in diabetic animals. Treatment of diabetic rats with GS did deteriorate the catabolic status seen in diabetes with increases in mortality as compared to diabetes alone. However, neither the overall pattern of enzyme synthesis seen in diabetic rats nor the alterations in CCK stimulated enzyme secretion were changed by treatment with GS. We conclude that the regulation of amylase synthesis and enzyme secretion by insulin is not mediated via GS.
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PMID:Pancreatic enzyme synthesis and secretion are independently regulated by insulin and glucocorticosteroids. 170 71

Transplantation of insulin secreting tissue as a free graft has the potential to become a safe and simple procedure to cure diabetes. However, clinical results, i.e. achievement of insulin independency, are poor, in spite of the use of immunosuppressive regimens, which are regularly successful in whole organ transplantation. In contrast to whole organ grafts, which are revascularized immediately after transplantation, free pancreatic islet grafts require the process of revascularization in order to establish a microvascular network, sufficient for the nutritional blood supply. We have demonstrated for the first time in vivo images of the process of revascularization of free islet xenografts including microvascular phenomena during graft rejection. Rat islet xenografts were isolated by collagenase digestion and transplanted into hamster dorsal skinfold chambers. After 6, 10 and 14 days the microvasculature of the islet grafts was analyzed by means of intravital fluorescence microscopy. Xenogeneic grafts were revascularized during the first 6 days similarly compared to syngeneic grafts; however, on day 10 after transplantation a reduction in size of the microvascular network as well as a decrease in functional capillary density and a reduction in capillary red blood cell velocity were observed, accompanied by microvascular rejection phenomena, such as an increase of microvascular permeability, edema formation, capillary widening and intravascular accumulation of white blood cells (WBCs) with concomitant WBC-endothelium interaction in post-capillary venules. Treatment with 2.5 mg/kg/d (+/-)-15-deoxyspergualin could not completely alleviate these microvascular rejection phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microvascular phenomena during pancreatic islet graft rejection. 171 22


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