RGD Reference Report - Defect in glucokinase translocation in Zucker diabetic fatty rats. - Rat Genome Database

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Defect in glucokinase translocation in Zucker diabetic fatty rats.

Authors: Fujimoto, Y  Donahue, EP  Shiota, M 
Citation: Fujimoto Y, etal., Am J Physiol Endocrinol Metab. 2004 Sep;287(3):E414-23. Epub 2004 May 11.
RGD ID: 1582633
Pubmed: PMID:15138155   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00575.2003   (Journal Full-text)

Hepatic glucose fluxes and intracellular movement of glucokinase (GK) in response to increased plasma glucose and insulin were examined in 10-wk-old, 6-h-fasted, conscious Zucker diabetic fatty (ZDF) rats and lean littermates. Under basal conditions, plasma glucose (mmol/l) and glucose turnover rate (GTR; micromol.kg(-1).min(-1)) were slightly higher in ZDF (8.4 +/- 0.3 and 53 +/- 7, respectively) than in lean rats (6.2 +/- 0.2 and 45 +/- 4, respectively), whereas plasma insulin (pmol/l) was higher in ZDF (1,800 +/- 350) than in lean rats (150 +/- 14). The ratio of hepatic uridine 5'-diphosphate-glucose 3H specific activity to plasma glucose 3H specific activity ([3H]UDP-G/[3H]G; %), total hepatic glucose output (micromol.kg(-1).min(-1)), and hepatic glucose cycling (micromol.kg(-1).min(-1)) were higher in ZDF (35 +/- 5, 87 +/- 16, and 33 +/- 10, respectively) compared with lean rats (18 +/- 3, 56 +/- 6, and 11 +/- 2, respectively). [3H]glucose incorporation into glycogen (micromol glucose/g liver) was similar in lean (1.0 +/- 0.7) and ZDF (1.6 +/- 0.8) rats. GK was predominantly located in the nucleus in both rats. With elevated plasma glucose and insulin, GTR (micromol.kg(-1).min(-1)), [3H]UDP-G/[3H]G (%), and [3H]glucose incorporation into glycogen (micromol glucose/g liver) were markedly higher in lean (191 +/- 22, 62 +/- 3, and 5.0 +/- 1.4, respectively) but similar in ZDF rats (100 +/- 6, 37 +/- 3, and 1.4 +/- 0.4, respectively) compared with basal conditions. GK translocation from the nucleus to the cytoplasm occurred in lean but not in ZDF rats. The unresponsiveness of hepatic glucose flux to the rise in plasma glucose and insulin seen in prediabetic ZDF rats was associated with impaired GK translocation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GckRattype 2 diabetes mellitus  IDA protein:altered localization:hepatocyte:impaired translocation from nucleus to cytoplasm in Zucker diabetic fatty ratsRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GckRatcarbohydrate phosphorylation  IDA  RGD 
GckRatglucose 6-phosphate metabolic process  IDA  RGD 
Gys2Ratglycogen biosynthetic process  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gys2Ratalpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity  IDA  RGD 
GckRatD-glucose binding  IDA  RGD 
GckRatglucokinase activity  IDA  RGD 
PyglRatglycogen phosphorylase activity  IDA  RGD 
Hk1Rathexokinase activity  IDA  RGD 
Hk2Rathexokinase activity  IDA  RGD 
Hk3Rathexokinase activity  IDA  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GCKHumanglycogen biosynthetic pathway   ISOGck (Rattus norvegicus) RGD 
GYS2Humanglycogen biosynthetic pathway   ISOGys2 (Rattus norvegicus) RGD 
GckMouseglycogen biosynthetic pathway   ISOGck (Rattus norvegicus) RGD 
GckRatglycogen biosynthetic pathway   IDA  RGD 
Gys2Mouseglycogen biosynthetic pathway   ISOGys2 (Rattus norvegicus) RGD 
Gys2Ratglycogen biosynthetic pathway   IDA  RGD 
G6PC1Humanglycogen degradation pathway   ISOG6pc1 (Rattus norvegicus) RGD 
G6pc1Mouseglycogen degradation pathway   ISOG6pc1 (Rattus norvegicus) RGD 
PYGLHumanglycogen degradation pathway   ISOPygl (Rattus norvegicus) RGD 
PyglRatglycogen degradation pathway   IDA  RGD 
PyglMouseglycogen degradation pathway   ISOPygl (Rattus norvegicus) RGD 
G6PC1Humanglycogen metabolic pathway  ISOG6pc1 (Rattus norvegicus) RGD 
G6pc1Mouseglycogen metabolic pathway  ISOG6pc1 (Rattus norvegicus) RGD 
GCKHumanglycogen metabolic pathway  ISOGck (Rattus norvegicus) RGD 
GYS2Humanglycogen metabolic pathway  ISOGys2 (Rattus norvegicus) RGD 
GckMouseglycogen metabolic pathway  ISOGck (Rattus norvegicus) RGD 
GckRatglycogen metabolic pathway  IDA  RGD 
Gys2Mouseglycogen metabolic pathway  ISOGys2 (Rattus norvegicus) RGD 
Gys2Ratglycogen metabolic pathway  IDA  RGD 
PYGLHumanglycogen metabolic pathway  ISOPygl (Rattus norvegicus) RGD 
PyglRatglycogen metabolic pathway  IDA  RGD 
PyglMouseglycogen metabolic pathway  ISOPygl (Rattus norvegicus) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Gck  (glucokinase)
Gys2  (glycogen synthase 2)
Hk1  (hexokinase 1)
Hk2  (hexokinase 2)
Hk3  (hexokinase 3)
Pygl  (glycogen phosphorylase L)

Genes (Mus musculus)
G6pc1  (glucose-6-phosphatase catalytic subunit 1)
Gck  (glucokinase)
Gys2  (glycogen synthase 2)
Pygl  (liver glycogen phosphorylase)

Genes (Homo sapiens)
G6PC1  (glucose-6-phosphatase catalytic subunit 1)
GCK  (glucokinase)
GYS2  (glycogen synthase 2)
PYGL  (glycogen phosphorylase L)

Objects referenced in this article
Gene G6pc1 glucose-6-phosphatase catalytic subunit 1 Rattus norvegicus
Gene Gckr glucokinase regulator Rattus norvegicus

Additional Information