000			nab a22 7a 4500
999			_c17860 _d17860
003			PC17860
005			20240531125415.0
008			240529b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_9763 _aEnríquez de Salamanca Lorente, Rafael _eInstituto de Investigación i+12
245	0	0	_aGlucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency. _h[artículo]
260			_bHuman molecular genetics, _c2016
300			_a25(7):1318-27.
500			_aFormato Vancouver: Collantes M, Serrano Mendioroz I, Benito M, Molinet Dronda F, Delgado M, Vinaixa M et al. Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency. Hum Mol Genet. 2016 Apr 1;25(7):1318-27.
501			_aPMID: 26908609
504			_aContiene 34 referencias
520			_aPorphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver.
710			_9625 _aInstituto de Investigación imas12
856			_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/1/pc17860.pdf _ySolicitar documento
942			_2ddc _cART _n0