title: Insulin injection restored increased insulin receptor substrate (IRS)-2 protein during short-term protein restriction but did not affect reduced insulin-like growth factor (IGF)-I mRNA or increased triglyceride accumulation in the liver of rats.
abstract: Dietary protein restriction reduces insulin-like growth factor (IGF)-I synthesis and impairs growth. Moreover, insulin secretion is impaired and hepatic insulin signaling is activated presumably through upregulation of insulin receptor substrate (IRS)-2, which can stimulate lipogenesis thereby resulting in steatosis. In order to determine whether impaired insulin secretion is the primary cause of these changes, we injected insulin into protein-restricted rats and compensated for the reduction in insulin secretion for 1 and 7 d. Insulin infusion did not overcome the reduction in liver IGF-I mRNA nor the hepatic triglyceride accumulation. In contrast, it clearly suppressed the upregulation of hepatic IRS-2 on day 1, but not on day 7. Furthermore, insulin elimination increased IRS-2 in H4IIE-C3 cells. In summary, we found that reduced insulin secretion during protein restriction directly increased hepatic IRS-2 as a rapid response on day 1, while additional mechanisms contributed to the upregulation of IRS-2 on day 7.
authors.affiliation: a Department of Agricultural Chemistry, School of Agriculture , Meiji University , Kawasaki , Japan.
authors.forename: Yori
authors.initials: Y
authors.lastname: Ozaki
authors.forename: Tomoya
authors.initials: T
authors.lastname: Takeda
authors.forename: Narumi
authors.initials: N
authors.lastname: Akanishi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hakuno
authors.forename: Yuka
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Asako
authors.initials: A
authors.lastname: Takenaka
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004044:Dietary Proteins / Q000032:analysis*; D007267:Injections; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D004044:Dietary Proteins; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D012333:RNA, Messenger; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I
keywords: insulin; insulin receptor substrate (IRS)-2; insulin-like growth factor (IGF)-I; low protein diet; protein malnutrition