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PMID: 14722613 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mosaic analysis of insulin receptor function.

The Journal of clinical investigation ·Vol. 113 ·No. 2 ·2004-01-00 ·Pages 209-19

Kitamura T, Kitamura Y, Nakae J, Giordano A, Cinti S, Kahn CR, Efstratiadis A, Accili D

Abstract

Insulin promotes both metabolism and growth. However, it is unclear whether insulin-dependent growth is merely a result of its metabolic actions. Targeted ablation of insulin receptor (Insr) has not clarified this issue, because of early postnatal lethality. To examine this question, we generated mice with variable cellular mosaicism for null Insr alleles. Insr ablation in approximately 80% of cells caused extreme growth retardation, lipoatrophy, and hypoglycemia, a clinical constellation that resembles the human syndrome of leprechaunism. Insr ablation in 98% of cells, while resulting in similar growth retardation and lipoatrophy, caused diabetes without beta-cell hyperplasia. The growth retardation was associated with a greater than 60-fold increase in the expression of hepatic insulin-like growth factor binding protein-1. These findings indicate that insulin regulates growth independently of metabolism and that the number of insulin receptors is an important determinant of the specificity of insulin action.

MeSH Terms
Adipose Tissue/metabolism Alleles Animals Blotting, Northern Blotting, Western Cell Division Genotype Hyperplasia Hypoglycemia/genetics Immunohistochemistry Insulin/metabolism Insulin-Like Growth Factor Binding Protein 1/metabolism Ligands Liver/metabolism Mice Mice, Transgenic Microscopy, Electron Mosaicism Phenotype Receptor, Insulin/genetics Reverse Transcriptase Polymerase Chain Reaction Time Factors
Chemicals
Insulin Insulin-Like Growth Factor Binding Protein 1 Ligands Receptor, Insulin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kitamura Tadahiro
Department of Medicine, College of Physicians & Surgeons of Columbia University, New York, New York 10032, USA.
Kitamura Yukari
Nakae Jun
Giordano Antonio
Cinti Saverio
Kahn C Ronald
Efstratiadis Argiris
Accili Domenico
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI17810
Published
2004-01-00
Pages
209-19
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC310748
Subset
IM
Grants
NIDDK NIH HHS · R01 DK058282 · United States
NIDDK NIH HHS · R37 DK058282 · United States
NIDDK NIH HHS · DK58282 · United States
External Links
PubMed source DOI: 10.1172/JCI17810 PMC Full Text View journal details
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