| Insulin-like growth factor 2 and the insulin receptor, but not insulin, regulate fetal hepatic glycogen synthesis. | |
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MedLine Citation:
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PMID: 20032056 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Whether insulin or IGFs regulate glycogen synthesis in the fetal liver remains to be determined. In this study, we used several knockout mouse strains, including those lacking Pdx-1 (pancreatic duodenal homeobox-1), Insr (insulin receptor), and Igf2 (IGF-II) to determine the role of these genes in the regulation of fetal hepatic glycogen synthesis. Our data show that insulin deficiency does not alter hepatic glycogen stores, whereas Insr and Igf2 deficiency do. We found that both insulin receptor isoforms (IR-A and IR-B) are present in the fetal liver, and their expression is gestationally regulated. IR-B is highly expressed in the fetal liver; nonetheless, the percentage of hepatic IR-A isoform, which binds Igf2, was significantly higher in the fetus than the adult. In vitro experiments demonstrate that Igf2 increases phosphorylation of hepatic Insr, insulin receptor substrate-2, and Akt proteins and also the activity of glycogen synthase. Igf2 ultimately increased glycogen synthesis in fetal hepatocytes. This increase could be blocked by the phosphoinositide 3-kinase inhibitor LY294008. Taken together, we propose Igf2 as a major regulator of fetal hepatic glycogen metabolism, the insulin receptor as its target receptor, and phosphoinositide 3-kinase as the signaling pathway leading to glycogen formation in the fetal liver. |
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Authors:
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Li Liang; Wei Hui Guo; Diego R Esquiliano; Masato Asai; Susana Rodriguez; Jodel Giraud; Jake A Kushner; Morris F White; Mary Frances Lopez |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-12-23 |
Journal Detail:
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Title: Endocrinology Volume: 151 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-26 Completed Date: 2010-02-26 Revised Date: 2011-07-22 |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 741-7 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine/Endocrine Division, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Crosses, Genetic DNA Primers Female Fetus / drug effects, physiology Glycogen Synthase / metabolism Hepatocytes / cytology, enzymology, physiology* Heterozygote Homeostasis Insulin / deficiency, genetics, physiology* Insulin-Like Growth Factor II / deficiency, genetics, physiology* Liver Glycogen / blood* Male Mice Mice, Knockout RNA, Messenger / genetics Receptor, Insulin / deficiency, genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM071046/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/Liver Glycogen; 0/RNA, Messenger; 11061-68-0/Insulin; 67763-97-7/Insulin-Like Growth Factor II; EC 2.4.1.11/Glycogen Synthase; EC 2.7.10.1/Receptor, Insulin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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