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  • 1
    ISSN: 1432-0428
    Keywords: Dihydroxyacetone ; ATP-sensitive K+ channels ; GK rat ; glycerol phosphate shuttle ; pancreatic beta cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the GK (Goto-Kakizaki) rat, a genetic model of non-insulin-dependent diabetes mellitus, glucose-induced insulin secretion is selectively impaired. In addition, it has been suggested by previous studies that impaired glucose metabolism in beta cells of the GK rat results in insufficient closure of ATP-sensitive K+ channels (KATP channels) and a consequent decrease in depolarization, leading to a decreased insulin release. We have recently reported that the site of disturbed glucose metabolism is probably located in the early stages of glycolysis or in the glycerol phosphate shuttle. In the present study, in order to identify the impaired metabolic step in diabetic beta cells, we have investigated insulin secretory capacity by stimulation with dihydroxyacetone (DHA), which is known to be directly converted to DHA-phosphate and to preferentially enter the glycerol phosphate shuttle. In addition, using the patch-clamp technique, we also have studied the sensitivity of DHA on the KATP channels of beta cells in GK rats. The insulin secretion in response to 5 mmol/l DHA with 2.8 mmol/l glucose was impaired, and DHA sensitivity of the KATP channels was reduced in beta cells of GK rats. From these results, we suggest that the intracellular site responsible for impaired glucose metabolism in pancreatic beta cells of GK rats is located in the glycerol phosphate shuttle.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Key words Insulin release ; intracellular calcium ; exocytosis ; GK rat ; permeabilized islets.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In spontaneously diabetic GK rats, insulin secretion from pancreatic beta cells in response to glucose is selectively impaired, probably due to deficient intracellular metabolism of glucose and impaired closure of KATP channels during glucose stimulation. By using electrically permeabilized islets of GK rats, we explored the functional modulations in exocytotic steps distal to the rise in [Ca2 + ]i in the diabetic condition. At 30 nmol/l Ca2 + (basal conditions) insulin release was similar between GK and non-diabetic control Wistar rats. In response to 3.0 μmol/l Ca2 + (maximum stimulatory conditions), insulin release was significantly augmented in permeabilized GK islets (p 〈 0.01). Raising glucose concentrations from 2.8 to 16.7 mmol/l further augmented insulin release induced by 3.0 μmol/l Ca2 + from permeabilized control islets(p 〈 0.001), but had no effect on that from permeabilized GK islets. The stimulatory effect of glucose on insulin release from permeabilized control islets was partly inhibited by 2,4-dinitrophenol, an inhibitor of mitochondrial oxidative phosphorylation (p 〈 0.01). The hyperresponse to Ca2 + in GK islets may play a physiologically compensatory role on the putative functional impairment both in [Ca2 + ]i rise and energy state in response to glucose in diabetic β cells, and may explain the relative preservation of insulin release induced by non-glucose depolarizing stimuli, such as arginine, from pancreatic islets in non-insulin-dependent diabetes mellitus. [Diabetologia (1995) 38: 772–778]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Key words Dihydroxyacetone ; ATP-sensitive K+ channels ; GK rat ; glycerol phosphate shuttle ; pancreatic beta cell.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the GK (Goto-Kakizaki) rat, a genetic model of non-insulin-dependent diabetes mellitus, glucose-induced insulin secretion is selectively impaired. In addition, it has been suggested by previous studies that impaired glucose metabolism in beta cells of the GK rat results in insufficient closure of ATP-sensitive K+ channels (KATP channels) and a consequent decrease in depolarization, leading to a decreased insulin release. We have recently reported that the site of disturbed glucose metabolism is probably located in the early stages of glycolysis or in the glycerol phosphate shuttle. In the present study, in order to identify the impaired metabolic step in diabetic beta cells, we have investigated insulin secretory capacity by stimulation with dihydroxyacetone (DHA), which is known to be directly converted to DHA-phosphate and to preferentially enter the glycerol phosphate shuttle. In addition, using the patch-clamp technique, we also have studied the sensitivity of DHA on the KATP channels of beta cells in GK rats. The insulin secretion in response to 5 mmol/l DHA with 2.8 mmol/l glucose was impaired, and DHA sensitivity of the KATP channels was reduced in beta cells of GK rats. From these results, we suggest that the intracellular site responsible for impaired glucose metabolism in pancreatic beta cells of GK rats is located in the glycerol phosphate shuttle. [Diabetologia (1994) 37: 1082–1087]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: Alkaline phosphatase ; Blood-brainbarrier ; Cytochemistry ; Endothelial cell ; Experimental allergic encephalomyelitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the functions of endothelial cell (ECs) in chronic relapsing experimental allergic encephalomyelitis (EAE), we examined ECs ultracytochemically in various stages of EAE, in conjunction with the localization of alkaline phosphatase (AP) activity. We also studied the relation between the specific localization of AP activity and pathological features at each stage. Chronic relapsing EAE was induced in strain-13 guinea pigs by inoculation with homologous myelin. Controls were inoculated with complete Freund's adjuvant. The controls showed AP activity on the luminal and abluminal surfaces of the plasmalemma, and in pinocytic vesicles and vesicular pits. The localization of AP activity in the preclinical stage of EAE was similar to that in control animals. The initial inflammatory and actively demyelinating stage with perivascular cuffs of mononuclear cells showed AP-positive reactions on the abluminal surface of the plasmalemma, and in vesicles and pits, but not on the luminal surface in many ECs. In a later stage showing relatively old plaques with perivascular accumulation of debris-containing macrophages, AP activity continued to show localization similar to that seen in the initial stage, except for the presence of AP activity on some segments of the abluminal plasmalemma. Inactive lesions with marked perivascular fibrosis showed no AP reaction products. AP activity in unaffected areas showed the same localization as that in control animals throughout the various clinical stages of EAE. These findings suggest that AP activity decreased as the inflammatory demyelination in EAE progressed. The gradual disappearance of AP activity suggests development of functional impairment of ECs.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 75 (1988), S. 337-344 
    ISSN: 1432-0533
    Keywords: Experimental allergic encephalomyelitis ; Serum thymic factor ; Suppressor T cell ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Acute experimental allergic encephalomyelitis (EAE) was induced in Hartley guinea pigs and Lewis rats, which were then treated with synthetic serum thymic factor (FTS). When a dose of 30 μg/100 g body weight of FTS was subcutaneously administered to the animals on days — 1 (before inoculation), 4, 9 and 15 intermittently, clinical symptoms of acute EAE were suppressed. Histopathological evaluation showed that the severity of EAE in FTS-treated guinea pigs was less than in unteated guinea pigs. Immunohistochemical examination showed that the numbers of OX6+, W3/25+, W3/13+ and OX19+ cells in FTS-treated rats were less than in untreated rats and that the number of OX8+ cells in FTS-treated rats was greater than in untreated rats. These findings suggest that FTS induced OX8+ cells in inflammatory lesions and suppressed inflammation in acute EAE.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0533
    Keywords: Experimental allergic encephalomyelitis ; Blood-brain barrier ; Na+, K+-Adenosine triphosphatase ; Basal lamina ; Horseradish peroxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We induced chronic relapsing experimental allergic encephalomyelitis (EAE), and studied the ultrastructural and ultracytochemical changes of the blood-brain barrier (BBB) in the demyelinating lesions of various stages of EAE. In the chronic, inactive stage with gliosis and perivascular fibrosis, the basal lamina (BL) of the perivascular processes of astrocytes was formed only partially, and neural parenchyma was not fully separated from the perivascular mesenchymal tissues by the BL of astrocytic processes. Vascular permeability of the BBB was studied using exogenous horseradish peroxidase (HRP) as the tracer: HRP extravasation was marked during the stages of both active myelin breakdown and removal of debris, and was recognized even at the inactive stage, although the degree was reduced to a very low level. The functions of the endothelia, assessed by ouabain-sensitive, K+-dependentp-nitrophenylphosphatase activity, were impaired as EAE progressed. The decrease in HRP leakage at the inactive stage suggests the endothelial impairment of active transport of metabolites including HRP. Along with the development of infammatory demyelination in EAE, the BBB in affected areas became more and more altered, and gradual morphological and functional impairment of the BBB developed.
    Type of Medium: Electronic Resource
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