IGF-1 receptor haploinsufficiency leads to age-dependent development of metabolic syndrome

Sachin Thakur, Neha Garg, Ning Zhang, Sophie E. Hussey, Nicolas Musi, Martin L Adamo

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)937-944
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume486
Issue number4
DOIs
StatePublished - May 13 2017

Keywords

  • Haploinsufficiency
  • IGF-1
  • IGF-1R
  • Igf1r
  • Insulin
  • Lipogenesis
  • Metabolic syndrome
  • SGA
  • Type 2 diabetes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'IGF-1 receptor haploinsufficiency leads to age-dependent development of metabolic syndrome'. Together they form a unique fingerprint.

  • Cite this