Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/48277
Title: Liver Glucokinase A456V induces potent hypoglycemia without dyslipidemia through a paradoxical induction of the catalytic subunit of glucose-6-phosphatase
Author: Vidal Alabró, Anna
Gómez Valadés, Alícia G.
Méndez Lucas, André
Llorens i Baucells, Jordi
Bartrons Bach, Ramon
Bermúdez i Mas, Jordi
Perales Losa, Carlos
Keywords: Glucocinasa
Fetge
Hipoglucèmia
Trastorns del metabolisme dels lípids
Diabetis
Glucokinase
Liver
Hypoglycemia
Lipid metabolism disorders
Diabetes
Issue Date: 2011
Publisher: Hindawi
Abstract: Recent reports point out the importance of the complex GK-GKRP in controlling glucose and lipid homeostasis. Several GK mutations affect GKRP binding, resulting in permanent activation of the enzyme. We hypothesize that hepatic overexpression of a mutated form of GK, GKA456V, described in a patient with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) and could provide a model to study the consequences of GK-GKRP deregulation in vivo. GKA456V was overexpressed in the liver of streptozotocin diabetic mice. Metabolite profiling in serum and liver extracts, together with changes in key components of glucose and lipid homeostasis, were analyzed and compared to GK wild-type transfected livers. Cell compartmentalization of the mutant but not the wild-type GK was clearly affected in vivo, demonstrating impaired GKRP regulation. GKA456V overexpression markedly reduced blood glucose in the absence of dyslipidemia, in contrast to wild-type GK-overexpressing mice. Evidence in glucose utilization did not correlate with increased glycogen nor lactate levels in the liver. PEPCK mRNA was not affected, whereas the mRNA for the catalytic subunit of glucose-6-phosphatase was upregulated ~4 folds in the liver of GKA456V-treated animals, suggesting that glucose cycling was stimulated. Our results provide new insights into the complex GK regulatory network and validate liver-specific GK activation as a strategy for diabetes therapy.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1155/2011/707928
It is part of: International Journal Of Endocrinology, 2011, num. 2011, p. 1-12
Related resource: http://dx.doi.org/10.1155/2011/707928
URI: http://hdl.handle.net/2445/48277
ISSN: 1687-8337
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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