Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Islets from male B10.BR mice (H-2k) were isolated by the collagenase technique, handpicked with a Pasteur pipette, and incubated (either intact or after dispersion with Dispase) for 0, 3, 5, 7, 10, or 14 days in tissue culture medium supplemented with either lymphokine supernatants or recombinant murine interferon-gamma. Islets and single cells were examined for IAk molecules by use of indirect immunofluorescence. Ia-positive islet cells were identified on the surface of islets incubated with 5-10% lymphokine for greater than 4 days or with 10, 100, or 1000 ng/ml interferon for greater than 6 days. Islets incubated in unsupplemented medium were Ia negative. Incubation with 5% lymphokine induced Ia expression on 10-40% dispersed islet cells cultured for greater than 9 days. Dual immunofluorescent staining for Ia and insulin revealed that Ia-positive cells included both beta- and non-beta-cells.
Diabetes 1986 Oct
PMID:Interferon-mediated induction of Ia antigen expression on isolated murine whole islets and dispersed islet cells. 309

Even without any immunologic barrier, as in autografts, reversal of diabetes induced by islets transplantation is not definitive and a secondary failure generally occurs. Factors involved in this failure were investigated in 13 male dogs undergoing total pancreatectomy and extemporaneous islets reinjection in the portal circulation. Five dogs died from postoperatory complications, three remained diabetic, and five were normoglycemic without insulin therapy for a duration of two to 26 weeks. Factors associated with failure appeared to be: (a) hemorrhage during dissection of pancreas prior to islets isolation, (b) imperfect collagenase digestion. Moreover, duration of this period of normoglycemia was negatively correlated with glycemia on the 20th postoperatory hour (r = 0.759, p less than 0.05), suggesting a possible relationship between glycemia and further graft outcome. Therefore, such a multifactorial statistical analysis seems to be helpful for the study of multiple technical parameters associated with the prognosis of islets transplantations.
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PMID:Secondary failure of islets autotransplantation in totally pancreatectomized dogs: a multifactorial study. 313 90

In order to establish a model for the in vivo assessment of islet function we have used the Rowett nude rat with transplantation of allogeneic and xenogeneic (mouse) islets into the renal subcapsular space following a minimal period of diabetic induction. Thirty-one nude rats were given streptozotocin and 30 became diabetic with blood glucose levels of greater than 20 mmol/l at 48 h. Rat and mouse islets were prepared by intraductal collagenase and bovine serum albumin density gradient isolation. Eight rats received transplants of freshly prepared allogeneic islets and 8 rats received transplants of 48 h cultured allogeneic islets. Seven rats received transplants of 48 h cultured mouse islets. Diabetes was reversed in all animals and all remained normoglycaemic for 21 days. Graft removal by nephrectomy resulted in hyperglycaemia in 22 out of 23 animals. Histological examination of the grafts showed a band of endocrine tissue beneath the renal capsule which stained strongly positive for insulin and there was no evidence of lymphocytic infiltration/rejection. One rat remained normoglycaemic after graft removal, which may represent recovery of the animal's own islets from the streptozotocin-induced diabetes. Control rats remained diabetic until death. In conclusion, the athymic nude rat can be used for the assessment of allogeneic and xenogeneic islet function when a short (48 h) period of streptozotocin-induced diabetes is used. This model offers a potential method for assessing in vivo function of isolated human islets.
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PMID:In vivo assessment of isolated pancreatic islet viability using the streptozotocin-induced diabetic nude rat. 313 50

Nine of 38 islet isolation experiments, using the duct collagenase technique, were selected for quality checks on isolated islet tissue. Pancreas was harvested, following aortic multi-organ perfusion. The total number of islets isolated amounted to 112,461 +/- 11,828 in 13.7 ml of suspension on average. In vitro secretion of beta cells was increased by a factor of 3.8 in response to glucose stimulation. Isolated islets in morphologically intact condition were detected by histological investigations. A new viability test (MTT, Sigma) for isolated pancreas islets worked well, in that it provided very soon information on islet survival in the wake of collagenase preparation. These results produced evidence to an improvement of technical conditions for clinical use of adult islet transplantation in cases of type I diabetes.
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PMID:[Isolation of islands of Langerhans from the human adult pancreas]. 314 48

Diabetes mellitus is associated with a generalized defect in connective tissue metabolism, including decreased growth, poor wound healing, and osteopenia. To determine the role of circulating factors in the etiology of these defects, we studied the effects of diabetic rat serum (DRS) on collagen, the major protein component of connective tissues. After preincubation of costal cartilage from hypophysectomized rats with experimental serum for 20 hours, [3H] proline was added for final four hours of incubation. Collagen and noncollagen protein were quantitated using purified bacterial collagenase. Compared to incubation of tissue in buffer without added serum, collagen production in cartilage incubated with 2% DRS was decreased by 23% (P less than .05), and with 4% serum by 88% (P less than .01). In contrast, serum from normal rats (NRS) increased collagen to 158% above buffer-incubated cartilage at 1.0% (P less than .02) and to 196% at 2% serum (P less than .01). Noncollagen protein production decreased below buffer only after addition of 2% or more DRS and increased above buffer after addition of 2% or more of NRS (178%, P less than .05). Addition of insulin at 10 and 100 mU/mL to DRS did not reverse defective collagen production, and addition of glucose (up to 900 mg/dL) or ketones (20 mmol/L) to NRS did not induce the changes in collagen production seen after addition of diabetic serum. Chromatographic separation of serum revealed that the inhibitory activity of DRS was in the high molecular weight fraction (less than 5000).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Direct inhibition of collagen production in vitro by diabetic rat serum. 328 35

Antigen expression is studied corresponding to a monoclonal autoantibody (IC2) derived from a hybridoma of rat myeloma Y3 cells and splenocytes of the diabetic BB rat. The selective reactivity of IC2 with islet cells has earlier been proven. We studied the possible specificity for beta islet cells, and the possible variation in autoantigen expression. Islet cells were isolated by cautious collagenase and dispase treatment. The cells were labelled with IC2 alone or together with anti-insulin immunoglobulin in double-labelling experiments. Extensive series of cells were examined by immunofluorescence microscopy, and some samples also by flow cytometry. In double-labelling examinations we found that only anti-insulin positive cells could bind the IC2 antibody, thus showing beta-cell selectivity. On the other hand, not all anti-insulin positive cells were IC2-positive. Since insulin treatment has been shown to decrease the incidence of diabetes in the BB rat, islet cells were examined after reduced beta-cell strain. Islet cells from Lewis and Wistar Furth rats display 21.4 +/- 1.4% IC2-positive cells, while islet cells from 24-hour fasting animals showed 7.0 +/- 1.4% (p less than 0.0001). Similar results were seen for BALB/c mice (25.0 +/- 1.8% vs. 13.7 +/- 2.3%, p less than 0.002). Also, after a week of insulin treatment, autoantigen expression was significantly decreased. Thus, the IC2 antibody is beta-cell-specific, and expression of the corresponding cell surface antigen depends on the functional state of the beta-cells.
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PMID:Antigen expression of the pancreatic beta-cells is dependent on their functional state, as shown by a specific, BB rat monoclonal autoantibody IC2. 328 66

24 week old diabetic mice of the C57Bl/Ks (db/db) strain were treated with subcutaneous injections of Ultratard M.C. insulin at a dose of 40 mU/animal rising to 100 mU/animal after 12 weeks. The mean plasma insulin value was 146 +/- 20 microU/ml (n = 6). During this time, the mean body weight of the animals rose significantly (p less than 0.05) and the mean blood glucose concentration fell significantly (p less than 0.005) until a value 2-3 times normal was reached, the insulin dose was then adjusted empirically to maintain hyperglycaemia at this level. Pancreatic islets from these animals, untreated diabetic mice and normal (+/+) mice were isolated by collagenase digest and perifused with a modified Krebs-Ringer medium containing either 3 mmol/L or 15 mmol/L glucose. During glucose challenge, normal islets demonstrated the usual biphasic insulin response, but high glucose levels elicited no response from islets of untreated diabetic mice. Previous treatment of diabetic mice with insulin led to a restoration of the first phase of glucose mediated insulin secretion on perifusion and a significant increase (p less than 0.05) in the second phase. Such an improvement in beta-cell function in the face of prevailing hyperglycaemia, even allowing for the possible mediating effect of a 30% fall in blood glucose, was taken as further evidence for a direct action of exogenous insulin on the islets of diabetic mice.
Diabetes Res 1987 Jun
PMID:Evidence for a direct action of exogenous insulin on the pancreatic islets of diabetic mice: II. Prolonged insulin therapy before islet isolation and perifusion. 330 82

The human fetal pancreas represents a source of insulin-producing beta-cells with a potential for transplantation to diabetic patients. It has previously been shown that such cells can be viably maintained in tissue culture media containing fetal calf serum (FCS) and that these explants continue to synthesize and release insulin. In this study the effects of human serum (HS) on the growth and function of human fetal pancreatic explants have been compared with those of FCS. For this purpose, pancreatic glands, obtained after prostaglandin-induced abortions, were briefly exposed to collagenase, and the digest was cultured in RPMI-1640 medium plus 10% pooled HS or FCS. The outgrowth of isletlike cell clusters (ICCs) was monitored. In 31 of 58 consecutively explanted glands, development of ICCs was observed. In the presence of FCS the outgrowth of ICC took place on top of a fibroblast monocellular cell layer; HS effected less growth of fibroblasts and increased the formation of ICCs about sevenfold compared with explants from the same glands maintained in FCS. However, in the explant cultures with HS, the cell number per ICC, expressed as DNA content, was reduced by 50%. In both FCS and HS the insulin content of the medium showed great variability and progressively declined from day 2 to day 5. The medium glucagon concentration also decreased but not to the same extent as that of insulin. Immunocytochemical-stained ICCs showed insulin- and glucagon-positive cells scattered among most nonstained, presumably nonendocrine cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Dec
PMID:Tissue culture of human fetal pancreas. Effects of human serum on development and endocrine function of isletlike cell clusters. 331 88

Many of the chronic complications of diabetes mellitus involve defects in the connective tissue such as poor wound healing, diminished bone formation, and decreased linear growth. Because collagen is the major protein component of these connective tissues, we examined collagen production in diabetic rats as a probe of this generalized defect in connective tissue metabolism. Doses of streptozocin ranging from 35 to 300 mg/kg were used to induce diabetes of graded metabolic severity in rats. Parietal bone or articular cartilage was removed and incubated at 37 degrees C with 5 microCi L-[5-3H]proline for 2 h, and collagen and noncollagen protein production were quantitated after separation with purified bacterial collagenase. Within 2 wk after induction of diabetes, collagen production was significantly reduced in bone and cartilage from diabetic rats to 52% (P less than .01) and 51% (P less than .01) of control (buffer-injected) levels, respectively. In contrast, noncollagen protein production in bone and cartilage from diabetic animals was no different from in tissue from control rats. The correlation between collagen relative to total protein production (relative rate) and the degree of hyperglycemia was highly significant for both bone (r = -.77, P less than .001) and cartilage (r = -.87, P less than .001). Other factors found to correlate with altered collagen production were the duration of diabetes and the amount of weight loss. Thus, diabetes is associated with a marked decrease in collagen production, which was seen early after induction of diabetes and was specific when compared with noncollagen protein production. Cumulative effects of these marked changes in collagen production may contribute to the chronic connective tissue complications in diabetes.
Diabetes 1988 Apr
PMID:Decreased collagen production in diabetic rats. 337 83

Calcitonin is known to inhibit secretion of gastrin and insulin in vivo. The objective of this study was to determine whether calcitonin can act directly on pancreatic islets in vitro to inhibit insulin release. Isolated islets were obtained from collagenase-treated rat pancreas, and three peptides (gastrin-releasing peptide, cholecystokinin-8, bombesin) and glucose were used to stimulate insulin release. All agents caused a significant increase in insulin secretion and calcitonin inhibited these responses, but had no consistent effect on basal release. This study provides evidence that calcitonin is an effective inhibitor of insulin secretion and acts directly on islet tissue.
Diabetes 1986 Jan
PMID:Calcitonin inhibition of insulin release from isolated rat pancreatic islets. 351 Jan 39


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