RGD Reference Report - Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. - Rat Genome Database

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Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats.

Authors: Aitman, TJ  Glazier, AM  Wallace, CA  Cooper, LD  Norsworthy, PJ  Wahid, FN  Al-Majali, KM  Trembling, PM  Mann, CJ  Shoulders, CC  Graf, D  St Lezin, E  Kurtz, TW  Kren, V  Pravenec, M  Ibrahimi, A  Abumrad, NA  Stanton, LW  Scott, J 
Citation: Aitman TJ, etal., Nat Genet 1999 Jan;21(1):76-83.
RGD ID: 619666
Pubmed: PMID:9916795   (View Abstract at PubMed)
DOI: DOI:10.1038/5013   (Journal Full-text)

The human insulin-resistance syndromes, type 2 diabetes, obesity, combined hyperlipidaemia and essential hypertension, are complex disorders whose genetic basis is unknown. The spontaneously hypertensive rat (SHR) is insulin resistant and a model of these human syndromes. Quantitative trait loci (QTLs) for SHR defects in glucose and fatty acid metabolism, hypertriglyceridaemia and hypertension map to a single locus on rat chromosome 4. Here we combine use of cDNA microarrays, congenic mapping and radiation hybrid (RH) mapping to identify a defective SHR gene, Cd36 (also known as Fat, as it encodes fatty acid translocase), at the peak of linkage to these QTLs. SHR Cd36 cDNA contains multiple sequence variants, caused by unequal genomic recombination of a duplicated ancestral gene. The encoded protein product is undetectable in SHR adipocyte plasma membrane. Transgenic mice overexpressing Cd36 have reduced blood lipids. We conclude that Cd36 deficiency underlies insulin resistance, defective fatty acid metabolism and hypertriglyceridaemia in SHR and may be important in the pathogenesis of human insulin-resistance syndromes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Metabolic Syndrome  ISOCd36 (Rattus norvegicus)619666; 619666 RGD 
Metabolic Syndrome  IAGP 619666 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal adipocyte glucose uptake susceptibilityIAGP 619666compared to BN/CrlRGD 
abnormal lipolysis  IAGP 619666 RGD 
increased adipocyte glucose uptake  IAGP 619666compared to SHRRGD 
Objects Annotated

Genes (Rattus norvegicus)
Cd36  (CD36 molecule)

Genes (Mus musculus)
Cd36  (CD36 molecule)

Genes (Homo sapiens)
CD36  (CD36 molecule (CD36 blood group))

Strains
SHR.BN-(Il6-Npy)  (NA)
SHR/Ola  (NA)


Additional Information