title: High fat diet induced insulin resistance and glucose intolerance are gender-specific in IGF-1R heterozygous mice.
abstract: Interactions between genes and environment play a critical role in the pathogenesis of type 2 diabetes. Low birth weight, due to genetic and environmental variables affecting fetal growth, is associated with increased susceptibility to the development of type 2 diabetes and metabolic disorders in adulthood. Clinical studies have shown that polymorphisms in the Insulin-like growth factor 1 (IGF-1) gene or heterozygous mutations in IGF-1 and IGF-1 receptor (IGF-1R) genes, resulting in reduced IGF-1 action, are associated with low birth weight and post-natal growth. Mice lacking one of the IGF-1R alleles (Igf1r(+/-)) exhibit a 10% reduction in post-natal growth, and develop glucose intolerance (males) and insulin resistance (males and females) as they age. To investigate whether adverse environmental factors could accelerate the onset of the metabolic syndrome, we conducted a short duration intervention of high fat diet (HFD) feeding in male and female Igf1r(+/-) and wild-type (WT) control mice. The HFD resulted in insulin resistance, hyperglycemia, and impaired glucose tolerance in males of both genotypes whereas in females exacerbated diabetes was observed only in the Igf1r(+/-) genotype, thus suggesting a sexual dimorphism in the influence of obesity on the genetic predisposition to diabetes caused by reduced IGF-1 action.
authors.affiliation: Department of Biochemistry, The University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Garg
authors.forename: Sachin
authors.initials: S
authors.lastname: Thakur
authors.forename: C Alex
authors.initials: CA
authors.lastname: McMahan
authors.forename: Martin L
authors.initials: ML
authors.lastname: Adamo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D018955:CD36 Antigens / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D018149:Glucose Intolerance / Q000235:genetics*; D005951:Glucose Tolerance Test; D006579:Heterozygote; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D012727:Sex Characteristics; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D018955:CD36 Antigens; D004041:Dietary Fats; D007328:Insulin; D017526:Receptor, IGF Type 1