RGD Reference Report - Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats. - Rat Genome Database

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Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats.

Authors: Aitman, TJ  Gotoda, T  Evans, AL  Imrie, H  Heath, KE  Trembling, PM  Truman, H  Wallace, CA  Rahman, A  Dore, C  Flint, J  Kren, V  Zidek, V  Kurtz, TW  Pravenec, M  Scott, J 
Citation: Aitman TJ, etal., Nat Genet 1997 Jun;16(2):197-201
RGD ID: 61078
Pubmed: PMID:9171835   (View Abstract at PubMed)
DOI: DOI:10.1038/ng0697-197   (Journal Full-text)

Coronary heart disease, hypertension, non-insulin-dependent diabetes and obesity are major causes of ill health in industrial societies. Disturbances of carbohydrate and lipid metabolism are a common feature of these disorders. The bases for these disturbances and their roles in disease pathogenesis are poorly understood. The spontaneously hypertensive rat (SHR), a widely used animal model of essential hypertension, has a global defect in insulin action on glucose metabolism and shows reduced catecholamine action on lipolysis in fat cells. In our study we used cellular defects in carbohydrate and lipid metabolism to dissect the genetics of defective insulin and catecholamine action in the SHR strain. In a genome screen for loci linked to insulin and catecholamine action, we identified two quantitative trait loci (QTLs) for defective insulin action, on chromosome 4 and 12. We found that the major (and perhaps only) genetic determinant of defective control of lipolysis in SHR maps to the same region of chromosome 4. These linkage results were ascertained in at least two independent crosses. As the SHR strain manifests many of the defining features of human metabolic Syndrome X, in which hypertension associates with insulin resistance, dyslipidaemia and abdominal obesity, the identification of genes for defective insulin and catecholamine action in SHR may facilitate gene identification in this syndrome and in related human conditions, such as type-2 diabetes and familial combined hyperlipidaemia.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Gluco16RatInsulin Resistance  IDA  RGD 
Gluco17RatInsulin Resistance  IDA  RGD 
Gluco3RatMetabolic Syndrome  IAGP  RGD 
Gluco4RatMetabolic Syndrome  IAGP  RGD 
Gluco5RatMetabolic Syndrome  IAGP  RGD 
Gluco3Rattype 2 diabetes mellitus  IAGP  RGD 
Gluco4Rattype 2 diabetes mellitus  IAGP  RGD 
Gluco5Rattype 2 diabetes mellitus  IAGP  RGD 

1 to 12 of 12 rows
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Gluco16Ratabnormal adipocyte glucose uptake  IAGP  RGD 
Gluco17Ratabnormal adipocyte glucose uptake  IAGP  RGD 
Gluco3Ratabnormal adipocyte glucose uptake  IAGP  RGD 
Gluco4Ratabnormal adipocyte glucose uptake  IAGP  RGD 
Gluco5Ratabnormal circulating free fatty acids level  IAGP  RGD 
SHR/NCrukRatdecreased adipocyte glucose uptake inducedIAGPinsulincompared to WKY/NCruk strainRGD 
SHR/OlaRatdecreased adipocyte glucose uptake  IAGP compared to BN-LxRGD 
SHR/OlaRatdecreased circulating free fatty acids level  IAGP compared to BN-LxRGD 
SHR/NCrukRatdecreased fatty acids level inducedIAGPisoproterenolcompared to WKY/NCruk strainRGD 
SHR/NCrukRatdecreased retroperitoneal fat pad weight  IAGP compared to WKY/NCruk strainRGD 
SHR/NCrukRatincreased fat cell size  IAGP compared to WKY/NCruk strainRGD 
SHR/OlaRatincreased fat cell size  IAGP compared to BN-LxRGD 
1 to 12 of 12 rows


QTLs
Gluco16  (Glucose level QTL 16) Gluco17  (Glucose level QTL 17) Gluco3  (Glucose level QTL 3)
Gluco4  (Glucose level QTL 4) Gluco5  (Glucose level QTL 5)

Strains
SHR/NCruk  (Spontaneously Hypertensive Rat) SHR/Ola  (NA) WKY/NCruk  (NA)

Marker D12Mit8 D12Mit8 Rattus norvegicus
Marker D12Mgh1 D12Mgh1 Rattus norvegicus
Marker D4Arb13 D4Arb13 Rattus norvegicus
Strain BXH/Ipcv null Rattus norvegicus
Strain HXB/Ipcv null Rattus norvegicus
Strain SHR.WKY-(D12Rat1-D12Mit3)/Tja null Rattus norvegicus
Strain SHR.WKY-(D16Rat88-D16Rat15)/Tja null Rattus norvegicus
Strain SHR.WKY-(D4Rat143-D4Rat10)/Tja null Rattus norvegicus
Gene Slc4a2 solute carrier family 4 member 2 Rattus norvegicus