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Liver GlucokinaseA456V Induces Potent Hypoglycemia without Dyslipidemia through a Paradoxical Induction of the Catalytic Subunit of Glucose-6-Phosphatase
Joint Authors
Perales, José Carlos
Bermúdez, Jordi
Gómez-Valadés, Alícia G.
Bartrons, Ramon
Méndez-Lucas, Andrés
Vidal-Alabró, Anna
Llorens, Jordi
Source
International Journal of Endocrinology
Issue
Vol. 2011, Issue 2011 (31 Dec. 2011), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2011-12-13
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Vidal-Alabró, Anna& Gómez-Valadés, Alícia G.& Méndez-Lucas, Andrés& Llorens, Jordi& Bartrons, Ramon& Bermúdez, Jordi…[et al.]. 2011. Liver GlucokinaseA456V Induces Potent Hypoglycemia without Dyslipidemia through a Paradoxical Induction of the Catalytic Subunit of Glucose-6-Phosphatase. International Journal of Endocrinology،Vol. 2011, no. 2011, pp.1-12.
https://search.emarefa.net/detail/BIM-492207
Modern Language Association (MLA)
Vidal-Alabró, Anna…[et al.]. Liver GlucokinaseA456V Induces Potent Hypoglycemia without Dyslipidemia through a Paradoxical Induction of the Catalytic Subunit of Glucose-6-Phosphatase. International Journal of Endocrinology No. 2011 (2011), pp.1-12.
https://search.emarefa.net/detail/BIM-492207
American Medical Association (AMA)
Vidal-Alabró, Anna& Gómez-Valadés, Alícia G.& Méndez-Lucas, Andrés& Llorens, Jordi& Bartrons, Ramon& Bermúdez, Jordi…[et al.]. Liver GlucokinaseA456V Induces Potent Hypoglycemia without Dyslipidemia through a Paradoxical Induction of the Catalytic Subunit of Glucose-6-Phosphatase. International Journal of Endocrinology. 2011. Vol. 2011, no. 2011, pp.1-12.
https://search.emarefa.net/detail/BIM-492207
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-492207