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

The effect of glycosylation on susceptibility of skin collagen to collagenase digestion was studied in a skin sample obtained at autopsy from the interscapular region of a 24 year old white male who had died of an acute illness and who had no history of diabetes. Homogeneous suspensions of insoluble collagen were prepared, and were incubated in 50 mmol l-1 dextrose at pH 7.35 and 37 degrees C for 7 days. Non-enzymatic glycosylation measured by the weak acid hydrolysis/thiobarbituric acid method increased from 13.1 +/- 1.0 (n = 5) to 45.2 +/- 5.5 (n = 8) nmol fructose per 10 mg collagen (P less than 0.001). Digestion of collagen using clostridial collagenase was monitored by measuring (a) hydroxyproline content and (b) absorption at 206 nm of the supernatant after centrifugation to remove substrate. The rate of digestion was similar in glycosylated and control collagen. We conclude that the ketoamine link formed in non-enzymatic glycosylation does not increase the resistance of collagen to enzymatic digestion. The possibility remains that subsequent rearrangement of this link could be important in this respect.
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PMID:Effect of in vitro non-enzymatic glycosylation of human skin collagen on susceptibility to collagenase digestion. 299 Sep 36

To determine the nature of the pancreatic islet cell cholecystokinin (CCK) receptor, we studied CCK receptor binding and biologic activity in isolated rat pancreatic islets. Binding of 70 pM 125I-CCK to collagenase-prepared isolated rat pancreatic islets at 24 degrees C was one-half maximal after 5 min and maximal at 60 min. At 60 min, specific binding was 12% of total radioactivity per 100 micrograms islet protein; nonspecific binding (in the presence of 1 microM CCK 8) was less than 2% of total radioactivity. Unlabeled CCK 33 inhibited labeled hormone binding one-half maximally at 2 nM; Scatchard analysis showed one binding site (Kd, 2.3 +/- 0.4 nM; Bmax, 8.1 pmol/mg protein). The agonist selectivity of this binding site was: CCK 8 = CCK 33 greater than desulfated-CCK 8 greater than CCK 4. Two CCK antagonists were studied; N-carbobenzoxy-L-tryptophan was more potent than dibutyryl-cGMP. When the effect of CCK on insulin release from the islets was studied, the order of potency of CCK agonists and antagonists on insulin secretion was the same as the order of their ability to inhibit 125I-CCK binding. The effect of CCK on insulin secretion was dependent on the glucose concentration in the media. CCK had no effect at 5.6 mM glucose and was fully effective at 11.0 mM glucose. These data, therefore, indicate that: specific binding sites for CCK are present in rat pancreatic beta cells; and CCK acts in concert with glucose to stimulate insulin secretion.
Diabetes 1986 Jan
PMID:Evidence that cholecystokinin interacts with specific receptors and regulates insulin release in isolated rat islets of Langerhans. 300 Aug 56

Monolayer cell cultures were obtained from a human insulinoma (HIN) after collagenase digestion. HIN cells were initially plated on extracellular matrix (ECM) secreted by bovine corneal endothelial cells. Capsular integrity from cell clusters quickly interrupted and cell began to migrate as adhesive sheets onto ECM. After 2 months on ECM cell attachment and proliferation occurred on plastic allowing cloning of cells by limiting dilution. 9 clones were successfully cultured for 7 months with 20 subsequent passages. Immunoreactivity for insulin by indirect immunofluorescence typical secretory granules by electron microscopy and stable amounts of immunoreactive insulin in culture media suggest that HIN cells are beta cell related. One clone HIN D8 when challenged for half an hour with either 30 mM glucose, 1 mM isobutyl Methylxanthine 4 mM Tolbutamide, 10(-6) M glucagon responded respectively with a 1.5, 2, 3 and 1.5 fold increase in insulin output. Population doubling time of HIN D8 was 42 hrs. Establishment of such insulin secreting cell lines provides a valuable tool for diabetes research.
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PMID:[Morphologic and functional study of a human insulin-secreting cell line]. 302 94

Large quantities of viable human islet tissue (beta cells) are required for transplant and for investigations of the autoimmune basis of Type I diabetes. Fetal pancreas offers a potential advantage over other possible sources of beta cells in that it retains some capacity for growth in vitro. We have cultured a total of 45 human pancreata from fetuses of gestational ages from 18 to 23 weeks. Each pancreas was obtained within minutes after delivery and usually cultured within 30 minutes. Pancreata were dispersed and cultured for up to 32 days. Maintenance and growth of the beta cells was assessed by the content of insulin in extracts of cultured tissue. As has been reported by others, fetal human beta cells survived in vitro for over 4 weeks. In three experiments in which a direct comparison was made, collagenase digestion of the fetal pancreas resulted in a significantly greater loss of insulin content compared to minced tissue cultured without digestion. Storage of three pancreata in medium overnight at 4 degrees C significantly reduced the insulin content of the pancreas compared to pancreata cultured immediately. During culture, the majority of the beta cells (based on insulin content) were found in small, macroscopic clumps attached to the surface of the culture dish, and surrounded by a nearly confluent monolayer of fibroblastoid cells. There was a marked decrease in the insulin content of the tissue during culture, most of it (to less than 25% of the original) occurring over the first 4-6 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maintenance of fetal human pancreatic beta cells in tissue culture. 302 65

Tetracyclines (including the semi-synthetic analogues, minocycline and doxycycline) are considered useful adjuncts in periodontal therapy because they suppress Gram-negative periodontopathogens. Recently, these antibiotics were found to inhibit mammalian collagenase activity, a property which may also be of therapeutic value. It has been suggested that the anti-collagenase properties of the tetracyclines are independent of their antibiotic efficacy. To advance this hypothesis further, we chemically converted tetracycline hydrochloride to its non-antimicrobial analogue, de-dimethylaminotetracycline. This chemically-modified tetracycline (CMT), although no longer an effective antibiotic, was found to inhibit the in vitro activity of collagenase from partially purified extracts of human rheumatoid synovial tissue and rachitic rat epiphysis. In a preliminary in vivo study, pathologically-excessive collagenase in skin and gingiva was induced by rendering adult male rats diabetic, and the oral administration of CMT to these rats significantly reduced the excessive collagenase activity in both tissues. Moreover, CMT administration did not affect the severe hyperglycemia in these rats but did prevent, at least in part, the diabetes-induced loss of body weight, skin weight, and skin collagen mass; these effects suggest a lack of toxicity in this animal model. A proposed clinical advantage of CMT over conventional tetracyclines, in the treatment of diseases characterized by excessive collagenolytic activity, is the lack of development of antibiotic-resistant micro-organisms during prolonged use. However, the consideration of clinical trials to support this hypothesis must await further laboratory and extensive toxicity tests.
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PMID:A non-antibacterial chemically-modified tetracycline inhibits mammalian collagenase activity. 304 Aug 32

Insulin has been reported to degrade inside the islets and islet lysosomal proteases have been thought to take part. As chloroquine is regarded as a potent lysosomotropic agent, an attempt has been made to see whether chloroquine has an influence on intrainsular degradation of insulin. After preculture of collagenase-isolated rat islets at 11 mM glucose together with [3H]leucine for 3 days for labelling newly synthesized insulin, islets were cultured for 1 day at 2.2 or 22 mM glucose with or without 0.02 mM chloroquine. Afterwards, radioactivity was measured in the proinsulin/insulin fraction. For control, the influence of chloroquine during 3-h incubation of both freshly isolated and precultured islets was also studied. During the 1-day culture at 2.2 mM glucose, prelabelled insulin was degraded significantly and addition of chloroquine did not alter the amount of insulin degraded. At 22 mM glucose, no significant amount of insulin had been degraded. During the 3-h incubation of freshly isolated as well as precultured islets, chloroquine was found to inhibit significantly glucose-induced biosynthesis of insulin. Glucose-induced release of insulin, however, was not influenced by chloroquine. It is concluded that chloroquine does not influence glucose-induced release or intra-insular degradation of insulin, but it interferes with the biosynthesis of insulin.
Diabetes Res Clin Pract 1988 May 19
PMID:Effect of chloroquine on biosynthesis, release and degradation of insulin in isolated islets of rat pancreas. 304 45

The effects of recombinant human growth hormone (GH, 1 micrograms/ml) and insulin-like growth factor I (IGF-I, 200 ng/ml) on the production of insulin and glucagon by human fetal islet-like cell clusters (ICCs) were studied in tissue culture. ICCs were derived after collagenase digestion and culture of pancreases from 16 fetuses (mean gestational age 15.6 wk). The ICCs were cultured with or without GH or IGF-I for 7 or 31 days. Basal rates of insulin and glucagon production were not altered by GH during the first 17 days of culture, but the release of both hormones was increasingly augmented by GH during the last 2 wk of culture (131% increase in insulin and 85% in glucagon compared with controls). ICCs cultured for 7 days in the presence of GH secreted more insulin when incubated for 120 min in 20 mM than in 2 mM glucose (2.1-fold response, P less than .05), whereas ICCs maintained in basal medium did not respond to glucose. GH had no effect on DNA and insulin content or insulin biosynthesis. Exogenous IGF-I caused a 28% suppression of insulin release (P less than .05) between days 4 and 10 of culture but induced a 49% increase in the mean secretion rate during the last week (days 25-31, P less than .01). Glucagon release was not affected by exogenous IGF-I. In contrast to GH, exogenous IGF-I induced a twofold increase in the DNA content of the 7-day--cultured ICCs. However, insulin biosynthesis and release were markedly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 Dec
PMID:Effects of growth hormone and insulin-like growth factor I on endocrine function of human fetal islet-like cell clusters during long-term tissue culture. 305 61

Using islets obtained by collagenase digestion, we have carried out a longitudinal study of the ultrastructure of endocrine cells of the islets of Langerhans from C57BL/6 mice, during the development of diabetes induced by the multiple low-dose streptozotocin (mld STZ) technique, with and without co-treatment with complete Freund's adjuvant (CFA). Diabetes, as assessed by glycemia, occurred on different days in the various treatment groups following the initial STZ injection. It was observed on day 7 in 4/7 and 3/7 animals treated with mld STZ and with CFA plus mld STZ respectively, on day 14 in 3/6 animals treated with CFA plus sub mld STZ and on day 21 in 2/5 animals treated with sub mld STZ. Breakages in the basement membrane of the B-cell, and severe vacuolation, occurred in all STZ treated animals, despite normoglycemia in animals in the sub-mld group. Mononuclear cells (macrophages acutely and lymphocytes chronically) were observed in islets from animals with mld STZ irrespective of treatment with CFA, but were found adjacent to acinar cells only in those animals treated with CFA. Damage to acinar cells was observed exclusively in this group. In sub mld STZ treated animals, mononuclear cells were found only in those animals treated with CFA. These findings are discussed with reference to the etiopathology of the disease.
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PMID:A longitudinal ultrastructural study of pancreatic cellular damage in murine streptozotocin diabetes. 307 Oct 64

The effect of cyclosporin-A, low-temperature culture, and anti-Ia antibodies on prevention of rejection of rat islet allografts was determined. Wistar-Furth islets were isolated by the collagenase technique and transplanted via the portal vein into diabetic Lewis recipients. Cyclosporin-A (30 mg/kg) injected at 0, 1, and 2 days after transplantation produced a significant prolongation of survival of the islet allografts (MST greater than 35.7 +/- 7.0 days) when hand-picked donor islets were used, whereas only a modest prolongation of survival (14.0 +/- 1.6 days) was obtained using donor islets removed directly from Ficoll gradients. This difference in survival was apparently due to the large number of lymphoid, antigen-presenting cells that were present in the islet fraction removed directly from the Ficoll gradients. Treatment of donor, hand-picked islets with a mixture of cross-reactive anti-Ia antibodies and complement without cyclosporin-A therapy did not prolong the survival of islet allografts (MST, 6.5 +/- 0.4 days versus 7.0 +/- 0.5 days in controls). In contrast, treatment of the donor islets with the mixture of anti-Ia antibodies and complement in conjunction with the 3-day course of cyclosporin-A therapy produced an 83% survival of the islet allografts at 60 days after transplantation. In vitro culture of hand-picked donor islets at 24 degrees C for 7 days and the 3-day course of cyclosporin-A therapy produced a 100% survival of the allografts at 60 days after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Jan
PMID:The effect of cyclosporin-A, low-temperature culture, and anti-Ia antibodies on prevention of rejection of rat islet allografts. 307 14

Storage of pancreatic islets by cryopreservation would greatly facilitate a large scale program of clinical islet transplantation. We report success on long-term follow-up with autotransplantation of frozen/thawed canine pancreatic fragments. Total pancreatectomy and islet isolation by collagenase ductal perfusion and mechanical disruption preceded either acute autotransplantation or cryogenic preservation prior to autotransplantation. Cryopreservation was by dimethylsulfoxide equilibration, cooling at 0.25 degrees C/min to -75 degrees C, storage in liquid N2 and thawing at 3.5 degrees C/min. Four of five acutely autotransplanted dogs remained normoglycemic for 20 months, with three of four maintaining normal K values on intravenous glucose tolerance test (IVGTT) and nondiabetic values on oral GTT. Four of four dogs transplanted with frozen/thawed islets remained normoglycemic for 15 months with three of four maintaining nondiabetic IV GTT K values and normal oral GTTs for 15 months. Both acutely transplanted and frozen/thawed islets are capable of maintaining long-term metabolic control. Cryopreservation preserved viability of sufficient canine pancreatic islets to reverse diabetes with autotransplantation. Function of the frozen-thawed islets showed minimal deterioration during a follow-up of 15 to 18 months.
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PMID:Long-term normoglycemia in pancreatectomized dogs transplanted with frozen/thawed pancreatic islets. 308 86


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