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Enrichment of hepatic glycogen and plasma glucose from H₂18 O informs gluconeog...

Coelho, Margarida; Mahar, Rohit; Belew, Getachew D.; Torres, Alejandra; Barosa, Cristina; Cabral, Fernando; Viegas, Ivan; Gastaldelli, Amalia

Deuterated water (2 H2 O) is a widely used tracer of carbohydrate biosynthesis in both preclinical and clinical settings, but the significant kinetic isotope effects (KIE) of 2 H can distort metabolic information and mediate toxicity. 18 O-water (H2 18 O) has no significant KIE and is incorporated into specific carbohydrate oxygens via well-defined mechanisms, but to date it has not been evaluated in any animal...


Determining the contribution of a high-fructose corn syrup formulation to hepat...

DiNunzio, Giada; Belew, Getachew D.; Torres, Alejandra N.; Silva, Joao Gabriel; Silva, Luís P.; Barosa, Cristina; Tavares, Ludgero; Jones, John G.

Excessive sugar intake including high-fructose corn syrup (HFCS) is implicated in the rise of obesity, insulin resistance and non-alcoholic fatty liver disease. Liver glycogen synthesis is influenced by both fructose and insulin signaling. Therefore, the effect of HFCS on hepatic glycogenesis was evaluated in mice feeding ad-libitum. Using deuterated water: the fraction of glycogen derived from triose-P sources...


Sources of hepatic glycogen synthesis in mice fed with glucose or fructose as t...

Jarak, Ivana; Barosa, Cristina; Martins, Fátima O.; Silva, Joao C. P.; Santos, Cristiano; Belew, Getachew Debas; Rito, João; Viegas, Ivan

The positional analysis of hepatic glycogen enrichment from deuterated water (2 H2 O) by 2 H NMR has been applied previously to resolve the contributions of glucose and fructose to glycogen synthesis in rodents fed a high sucrose diet. To further validate this method, this analysis was applied to mice fed with synthetic diets whose carbohydrate components consisted solely of either glucose or fructose.; The aut...


Hepatic anaplerotic outflow fluxes are redirected from gluconeogenesis to lacta...

Jones, John G.; Garcia, Paula; Barosa, Cristina; Delgado, Teresa C.; Diogo, Luísa

http://www.sciencedirect.com/science/article/B6WN3-4VJ0DT5-1/2/787b10f4d5c8351d470d0ee77de680d4


Quantification of hepatic transaldolase exchange activity and its effects on tr...

Jones, John G.; Garcia, Paula; Barosa, Cristina; Delgado, Teresa C.; Caldeira, M. Madalena; Diogo, Luísa

Exchange of hepatic glucose-6-phosphate (G6P) and glyceraldehyde-3-phosphate via transaldolase modifies hepatic G6P enrichment from glucose or gluconeogenic tracers. Transaldolase exchange was quantified in five healthy, fed subjects following an oral bolus of [1,2,3-13C3]glycerol (25-30 mg/kg) and paracetamol (10-12 mg/kg). 13C Isotopomers of hepatic G6P were quantified by 13C NMR spectroscopy of urinary glucu...


Metabolic characterisation of plasma in juveniles with glycogen storage disease...

Duarte, Iola F.; Goodfellow, Brian J.; Barros, António; Jones, John G.; Barosa, Cristina; Diogo, Luísa; Garcia, Paula; Gil, Ana M.

This paper reports the first application of high-resolution 1H NMR spectroscopy to the plasma of five juveniles with glycogen storage disease type 1a (GSD1a), permitting the characterisation of the plasma metabolic profile and the identification of alterations relative to a set of control samples. The relaxation-weighted spectra allowed changes in low molecular weight compounds to be detected more clearly, wher...


Noninvasive analysis of hepatic glycogen kinetics before and after breakfast wi...

Jones, John G.; Fagulha, Ana; Barosa, Cristina; Bastos, Margarida; Barros, Luisa; Baptista, Carla; Caldeira, M. Madalena; Carvalheiro, Manuela

The contributions of hepatic glycogenolysis to fasting glucose production and direct pathway to hepatic glycogen synthesis were quantified in eight type 1 diabetic patients and nine healthy control subjects by ingestion of (2)H(2)O and acetaminophen before breakfast followed by analysis of urinary water and acetaminophen glucuronide. After overnight fasting, enrichment of glucuronide position 5 relative to body...


Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: A simple analysis by 1...

Mendes, Ana C.; Caldeira, M. Madalena; Silva, Cláudia; Burgess, Shawn C.; Merritt, Matthew E.; Gomes, Filipe; Barosa, Cristina; Delgado, Teresa C.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-13C]glucose. Glucuronide 13C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of 13C-13C spin-coupled multiplet components within each 13C resonance by 13C NMR. The [U-13C]glucuronide isotopomer derived...


Simple measurement of gluconeogenesis by direct 2H NMR analysis of menthol gluc...

Ribeiro, Angela; Caldeira, M. Madalena; Carvalheiro, Manuela; Bastos, Margarida; Baptista, Carla; Fagulha, Ana; Barros, Luisa; Barosa, Cristina

The contribution of gluconeogenesis to fasting glucose production was determined by a simple measurement of urinary menthol glucuronide (MG) 2H enrichment from 2H2O. Following ingestion of 2H2O (0.5% body water) during an overnight fast and a pharmacological dose (400 mg) of a commercial peppermint oil preparation the next morning, 364 mumol MG was quantitatively recovered from a 2-h urine collection by ether e...


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