RGD Reference Report - Mosaic analysis of insulin receptor function. - Rat Genome Database

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Mosaic analysis of insulin receptor function.

Authors: Kitamura, T  Kitamura, Y  Nakae, J  Giordano, A  Cinti, S  Kahn, CR  Efstratiadis, A  Accili, D 
Citation: Kitamura T, etal., J Clin Invest 2004 Jan;113(2):209-19.
RGD ID: 1302525
Pubmed: PMID:14722613   (View Abstract at PubMed)
PMCID: PMC310748   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI17810   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Insr  (insulin receptor)

Genes (Mus musculus)
Insr  (insulin receptor)

Genes (Homo sapiens)
INSR  (insulin receptor)

Objects referenced in this article
Gene Foxo1 forkhead box O1 Mus musculus
Gene Igfbp1 insulin-like growth factor binding protein 1 Mus musculus

Additional Information