Alteration of de novo glucose production contributes to fasting hypoglycaemia in Fyn deficient mice

Yingjuan Yang, Elena Tarabra, Gong She Yang, Bhavapriya Vaitheesvaran, Gustavo Palacios, Irwin J. Kurland, Jeffrey E. Pessin, Claire C. Bastie

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Previous studies have demonstrated that glucose disposal is increased in the Fyn knockout (FynKO) mice due to increased insulin sensitivity. FynKO mice also display fasting hypoglycaemia despite decreased insulin levels, which suggested that hepatic glucose production was unable to compensate for the increased basal glucose utilization. The present study investigates the basis for the reduction in plasma glucose levels and the reduced ability for the liver to produce glucose in response to gluconeogenic substrates. FynKO mice had a 5-fold reduction in phosphoenolpyruvate carboxykinase (PEPCK) gene and protein expression and a marked reduction in pyruvate, pyruvate/lactate-stimulated glucose output. Remarkably, de novo glucose production was also blunted using gluconeogenic substrates that bypass the PEPCK step. Impaired conversion of glycerol to glucose was observed in both glycerol tolerance test and determination of the conversion of 13C-glycerol to glucose in the fasted state. α- glycerol phosphate levels were reduced but glycerol kinase protein expression levels were not changed. Fructose-driven glucose production was also diminished without alteration of fructokinase expression levels. The normal levels of dihydroxyacetone phosphate and glyceraldehyde-3- phosphate observed in the FynKO liver extracts suggested normal triose kinase function. Fructose-bisphosphate aldolase (aldolase) mRNA or protein levels were normal in the Fyn-deficient livers, however, there was a large reduction in liver fructose-6-phosphate (30-fold) and fructose-1,6- bisphosphate (7-fold) levels as well as a reduction in glucose-6-phosphate (2-fold) levels. These data suggest a mechanistic defect in the allosteric regulation of aldolase activity.

Original languageEnglish (US)
Article numbere81866
JournalPLoS One
Volume8
Issue number11
DOIs
StatePublished - Nov 28 2013

Fingerprint

hypoglycemia
Hypoglycemia
fasting
Glucose
glucose
mice
fructose-bisphosphate aldolase
Glycerol
Fructose-Bisphosphate Aldolase
glycerol
liver
Knockout Mice
Liver
Phosphoenolpyruvate
triokinase
fructokinase
Pyruvic Acid
fructose
glycerol kinase
protein synthesis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Yang, Y., Tarabra, E., Yang, G. S., Vaitheesvaran, B., Palacios, G., Kurland, I. J., ... Bastie, C. C. (2013). Alteration of de novo glucose production contributes to fasting hypoglycaemia in Fyn deficient mice. PLoS One, 8(11), [e81866]. https://doi.org/10.1371/journal.pone.0081866

Alteration of de novo glucose production contributes to fasting hypoglycaemia in Fyn deficient mice. / Yang, Yingjuan; Tarabra, Elena; Yang, Gong She; Vaitheesvaran, Bhavapriya; Palacios, Gustavo; Kurland, Irwin J.; Pessin, Jeffrey E.; Bastie, Claire C.

In: PLoS One, Vol. 8, No. 11, e81866, 28.11.2013.

Research output: Contribution to journalArticle

Yang, Yingjuan ; Tarabra, Elena ; Yang, Gong She ; Vaitheesvaran, Bhavapriya ; Palacios, Gustavo ; Kurland, Irwin J. ; Pessin, Jeffrey E. ; Bastie, Claire C. / Alteration of de novo glucose production contributes to fasting hypoglycaemia in Fyn deficient mice. In: PLoS One. 2013 ; Vol. 8, No. 11.
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