Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency

Human Molecular Genetics
María CollantesAntonio Fontanellas

Abstract

Porphobilinogen 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 bod...Continue Reading

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Citations

Nov 1, 2016·Indian Journal of Gastroenterology : Official Journal of the Indian Society of Gastroenterology·Sumant AroraAshwani K Singal
Mar 20, 2018·Internal and Emergency Medicine·Federica DepetriMaria Domenica Cappellini
May 20, 2020·International Journal of Molecular Sciences·Elena Di Pierro, Francesca Granata
Aug 31, 2021·Molecular Therapy. Nucleic Acids·Daniel JericóAntonio Fontanellas

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