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Titolo:
Effects of dichloroacetate (DCA) on serum insulin levels and insulin-controlled signaling proteins in livers of male B6C3F1 mice
Autore:
Lingohr, MK; Thrall, BD; Bull, RJ;
Indirizzi:
Washington State Univ, Pullman, WA 99164 USA Washington State Univ Pullman WA USA 99164 te Univ, Pullman, WA 99164 USA Pacific NW Natl Labs, Richland, WA 99352 USA Pacific NW Natl Labs Richland WA USA 99352 l Labs, Richland, WA 99352 USA
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 1, volume: 59, anno: 2001,
pagine: 178 - 184
SICI:
1096-6080(200101)59:1<178:EOD(OS>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEPATOMA-CELL LINE; GROWTH-FACTOR; TRICHLOROACETIC-ACID; MURINE HEPATOCYTES; DRINKING-WATER; RECEPTOR; RAT; MUTAGENICITY; MOUSE; HEPATOCARCINOGENESIS;
Keywords:
dichloroacetate; glycogen; insulin; signaling; insulin receptor PKB; hepatocarcinogen;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Bull, RJ MoBull Consulting, 8382 Gage Blvd,Suite O,Box 511, Kennewick, WA 99336 USA MoBull Consulting 8382 Gage Blvd,Suite O,Box 511 Kennewick WA USA99336
Citazione:
M.K. Lingohr et al., "Effects of dichloroacetate (DCA) on serum insulin levels and insulin-controlled signaling proteins in livers of male B6C3F1 mice", TOXICOL SCI, 59(1), 2001, pp. 178-184

Abstract

DCA is hepatocarcinogenic in rodents. At carcinogenic doses, DCA causes a large accumulation of liver glycogen, Thus, we studied the effects of DCA treatment on insulin levels and expression of insulin-controlled signaling proteins in the liver. DCA treatment (0.2-2.0 g/l in drinking water for 2 weeks) reduced serum insulin levels. The decrease persisted for at least 8 weeks. In livers of mice treated with DCA for 2-, 10-, and 52-week periods, insulin receptor (IR) protein levels were significantly depressed. Additionally, protein kinase B (PKB alpha) expression decreased significantly with DCA treatment. In normal liver, glycogen levels were increased as early as at 1 week, and this effect preceded changes in insulin and IR and PKB alpha. In contrast to normal liver, IR protein was elevated in DCA-induced liver tumors relative to that in liver tissue of untreated animals and to an evengreater extent when compared to adjacent normal liver in the treated animal. Mitogen-activated protein kinase (MAP kinase) phosphorylation was also increased in tumor tissue relative to normal liver tissue and tissue from untreated controls. These data suggest that normal hepatocytes down-regulate insulin-signaling proteins in response to the accumulation of liver glycogen caused by DCA. Futhermore, these results suggest that the initiated cell population, which does not accumulate glycogen and is promoted by DCA treatment, responds differently from normal hepatocytes to the insulin-like effects of this chemical. The differential sensitivity of the 2 cell populations may contribute to the tumorigenic effects of DCA in the liver.

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Documento generato il 04/04/20 alle ore 21:50:11