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Mitochondrial chang...
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Boquist, Lennart
(författare)
Mitochondrial changes and associated alterations induced in mice by streptozotocin administered in vivo and in vitro.
- Artikel/kapitelEngelska1987
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Elsevier,1987
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LIBRIS-ID:oai:DiVA.org:liu-113926
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-113926URI
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https://doi.org/10.1016/S0168-8227(87)80037-2DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Isolated mouse liver mitochondria incubated with streptozotocin showed decreased rate and extent of Ca2+ uptake, and, dependent on the concentration of streptozotocin and the addition of alpha-ketoglutarate, glutamate, fluorocitrate or guanosine 5'-triphosphate, the retention of Ca2+ was either increased or decreased. Similar observations were made in liver mitochondria incubated with succinyl-CoA. In mitochondria isolated from the kidneys and islets of mice injected with streptozotocin, with and without additional injections of glucose and/or glucagon, the rate and extent of Ca2+ uptake were reduced and the release of accumulated Ca2+ was stimulated. Electron microscopy and X-ray microanalysis showed dislocation of Ca2+-containing precipitates from the mitochondria to the cytosol, and stereology disclosed increased mitochondrial volume in the B cells of streptozotocin-treated mice. State 3 and state 4 respiration with NAD-linked substrates was inhibited, but succinate oxidation was unaffected, in mitochondria isolated from the kidneys of mice treated with streptozotocin. In the kidneys of streptozotocin-injected mice, the concentration of succinyl-CoA was increased, that of citrate and guanosine 5'-triphosphate was decreased, that of glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-diphosphate was unaffected, and the metabolite concentration ratios suggested increased mitochondrial [NAD+]/[NADH] ratio and decreased cytoplasmic [NAD+]/[NADH] ratio. It is suggested as a new hypothesis that the cytotoxicity and the diabetogenicity of streptozotocin are dependent on inhibited citric acid cycle enzyme activity (primarily that of succinyl-CoA synthetase and citrate synthetase) with altered metabolite concentrations, leading to impairment of the mitochondrial uptake of Ca2+ and the activation of the pyruvate, isocitrate and alpha-ketoglutarate dehydrogenases.
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Boquist, S
(författare)
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Alehagen, UrbanÖstergötlands Läns Landsting,Linköpings universitet,Kardiologi,Hälsouniversitetet,Kardiologiska kliniken US(Swepub:liu)urbal84
(författare)
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Linköpings universitetKardiologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Diabetes Research and Clinical Practice: Elsevier3:4, s. 179-1900168-82271872-8227
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