High fat diet induced insulin resistance and glucose intolerance are gender-specific in IGF-1R heterozygous mice

• Published in: Biochemical and biophysical research communications Vol. 413; no. 3; pp. 476 - 480
• Main Authors: Garg, Neha, Thakur, Sachin, Alex McMahan, C., Adamo, Martin L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30-09-2011
• Subjects: Animals; Blood Glucose - genetics; Body Weight - genetics; CD36 Antigens - genetics; Diet, High-Fat - adverse effects; Dietary Fats - administration & dosage; Dietary Fats - adverse effects; Female; Gene Expression; Genetic Predisposition to Disease; Glucose Intolerance - genetics; Glucose Tolerance Test; Heterozygote; HFD; IGF-1; IGF-1R; Igf1r; Insulin - blood; Insulin Resistance - genetics; Male; Mice; Mice, Mutant Strains; Receptor, IGF Type 1 - genetics; Sex Characteristics; Sex Factors; SGA; Type 2 diabetes; Type 2 diabetes; IGF-1; IGF-1R; Igf1r; SGA; HFD
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.08.123

► Interaction between genes and environment is critical in pathogenesis of diabetes. ► Reduced IGF-1 action is associated with low birth weight and post-natal growth. ► We examine effects of short duration HFD in male and female
Igf1r
+/−
and WT mice. ► Igf1r heterozygosity results in loss of resistance to HFD in the female gender.
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.