title: IGF-1 receptor haploinsufficiency leads to age-dependent development of metabolic syndrome.
abstract: Individuals born small for gestational age (SGA) are at a higher risk of developing the metabolic syndrome later in life. IGF-1 resistance has been reported in placentae from SGA births and mutations in the Igf1 receptor gene have been reported in several cohorts of SGA subjects. We have used the Igf1r heterozygous (Igf1r+/-) male mouse as a model to investigate the mechanisms by which Igf1r haploinsufficiency leads to insulin resistance. Despite exhibiting IGF-1 resistance, insulin signaling is enhanced in young Igf1r+/-mice but is attenuated in the muscle of old Igf1r+/-mice. Although smaller than WT (wild type) mice, old-aged Igf1r+/-had increased adiposity and exhibit increased lipogenesis. We hypothesize that IGF-1 resistance initially causes a transient increase in insulin signaling thereby promoting a lipogenic phenotype, which subsequently leads to insulin resistance.
authors.affiliation: Department of Biochemistry and Structural Biology, USA.
authors.forename: Sachin
authors.initials: S
authors.lastname: Thakur
authors.affiliation: Department of Biochemistry and Structural Biology, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Garg
authors.affiliation: Department of Medicine/Diabetes Division, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Medicine/Diabetes Division, USA.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Hussey
authors.affiliation: Department of Medicine/Diabetes Division, USA; The Sam and Ann Barshop Institute for Longevity and Aging Studies at the University of Texas Health Science Center at San Antonio, Texas 78229, USA; Geriatric Research, Education, and Clinical Center (GRECC), South Texas Veterans Health Care System, San Antonio, TX 78229, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Musi
authors.affiliation: Department of Biochemistry and Structural Biology, USA; The Sam and Ann Barshop Institute for Longevity and Aging Studies at the University of Texas Health Science Center at San Antonio, Texas 78229, USA. Electronic address: adamo@biochem.uthscsa.edu.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Adamo
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D057895:Haploinsufficiency / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D017526:Receptor, IGF Type 1 / Q000235:genetics*
chemical_list: D017526:Receptor, IGF Type 1
keywords: Haploinsufficiency; IGF-1; IGF-1R; Igf1r(+/-); Insulin; Lipogenesis; Metabolic syndrome; SGA; Type 2 diabetes