Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2000-11-15
pubmed:abstractText
Nonlinear interactions between obesity and genetic risk factors are thought to determine susceptibility to type 2 diabetes. We used genetic obesity as a tool to uncover latent differences in diabetes susceptibility between two mouse strains, C57BL/6J (B6) and BTBR. Although both BTBR and B6 lean mice are euglycemic and glucose tolerant, lean BTBR x B6 F1 male mice are profoundly insulin resistant. We hypothesized that the genetic determinants of the insulin resistance syndrome might also predispose genetically obese mice to severe diabetes. Introgressing the ob allele into BTBR revealed large differences in diabetes susceptibility between the strain backgrounds. In a population of F2-ob/ob mice segregating for BTBR and B6 alleles, we observed large variation in pancreatic compensation for the underlying insulin resistance. We also detected two loci that substantially modify diabetes severity, and a third locus that strongly links to fasting plasma insulin levels. Amplification of the genetic signal from these latent diabetes susceptibility alleles in F2-ob/ob mice permitted discovery of an interaction between the two loci that substantially increased the risk of severe type 2 diabetes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1946-54
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11078464-Alleles, pubmed-meshheading:11078464-Animals, pubmed-meshheading:11078464-Blood Glucose, pubmed-meshheading:11078464-Diabetes Mellitus, pubmed-meshheading:11078464-Diabetes Mellitus, Type 2, pubmed-meshheading:11078464-Fasting, pubmed-meshheading:11078464-Genetic Predisposition to Disease, pubmed-meshheading:11078464-Hyperinsulinism, pubmed-meshheading:11078464-Immunohistochemistry, pubmed-meshheading:11078464-Insulin, pubmed-meshheading:11078464-Insulin Resistance, pubmed-meshheading:11078464-Islets of Langerhans, pubmed-meshheading:11078464-Lod Score, pubmed-meshheading:11078464-Male, pubmed-meshheading:11078464-Mice, pubmed-meshheading:11078464-Mice, Inbred C57BL, pubmed-meshheading:11078464-Mice, Mutant Strains, pubmed-meshheading:11078464-Mice, Obese, pubmed-meshheading:11078464-Obesity
pubmed:year
2000
pubmed:articleTitle
Genetic obesity unmasks nonlinear interactions between murine type 2 diabetes susceptibility loci.
pubmed:affiliation
Department of Biochemistry, University of Wisconsin-Madison, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't