RGD Reference Report - Glucokinase is a critical regulator of ventromedial hypothalamic neuronal glucosensing. - Rat Genome Database

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Glucokinase is a critical regulator of ventromedial hypothalamic neuronal glucosensing.

Authors: Kang, L  Dunn-Meynell, AA  Routh, VH  Gaspers, LD  Nagata, Y  Nishimura, T  Eiki, J  Zhang, BB  Levin, BE 
Citation: Kang L, etal., Diabetes. 2006 Feb;55(2):412-20.
RGD ID: 1601297
Pubmed: PMID:16443775   (View Abstract at PubMed)

To test the hypothesis that glucokinase is a critical regulator of neuronal glucosensing, glucokinase activity was increased, using a glucokinase activator drug, or decreased, using RNA interference combined with calcium imaging in freshly dissociated ventromedial hypothalamic nucleus (VMN) neurons or primary ventromedial hypothalamus (VMH; VMN plus arcuate nucleus) cultures. To assess the validity of our approach, we first showed that glucose-induced (0.5-2.5 mmol/l) changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) oscillations, using fura-2 and changes in membrane potential (using a membrane potential-sensitive dye), were highly correlated in both glucose-excited and -inhibited neurons. Also, glucose-excited neurons increased (half-maximal effective concentration [EC(50)] = 0.54 mmol/l) and glucose-inhibited neurons decreased (half-maximal inhibitory concentration [IC(50)] = 1.12 mmol/l) [Ca(2+)](i) oscillations to incremental changes in glucose from 0.3 to 5 mmol/l. In untreated primary VMH neuronal cultures, the expression of glucokinase mRNA and the number of demonstrable glucosensing neurons fell spontaneously by half over 12-96 h without loss of viable neurons. Transfection of neurons with small interfering glucokinase RNA did not affect survival but did reduce glucokinase mRNA by 90% in association with loss of all demonstrable glucose-excited neurons and a 99% reduction in glucose-inhibited neurons. A pharmacological glucokinase activator produced a dose-related increase in [Ca(2+)](i) oscillations in glucose-excited neurons (EC(50) = 0.98 mmol/l) and a decrease in glucose-inhibited neurons (IC(50) = 0.025 micromol/l) held at 0.5 mmol/l glucose. Together, these data support a critical role for glucokinase in neuronal glucosensing.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GckRatintracellular glucose homeostasis  IMP  RGD 
GckRatregulation of glucose mediated signaling pathway  IMP in ventromedial hypothalamic neuronsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gck  (glucokinase)


Additional Information