RGD Reference Report - Transgenic rescue of insulin receptor-deficient mice. - Rat Genome Database

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Transgenic rescue of insulin receptor-deficient mice.

Authors: Okamoto, H  Nakae, J  Kitamura, T  Park, BC  Dragatsis, I  Accili, D 
Citation: Okamoto H, etal., J Clin Invest 2004 Jul;114(2):214-23.
RGD ID: 1302526
Pubmed: PMID:15254588   (View Abstract at PubMed)
PMCID: PMC449751   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI21645   (Journal Full-text)

The role of different tissues in insulin action and their contribution to the pathogenesis of diabetes remain unclear. To examine this question, we have used genetic reconstitution experiments in mice. Genetic ablation of insulin receptors causes early postnatal death from diabetic ketoacidosis. We show that combined restoration of insulin receptor function in brain, liver, and pancreatic beta cells rescues insulin receptor knockout mice from neonatal death, prevents diabetes in a majority of animals, and normalizes adipose tissue content, lifespan, and reproductive function. In contrast, mice with insulin receptor expression limited to brain or liver and pancreatic beta cells are rescued from neonatal death, but develop lipoatrophic diabetes and die prematurely. These data indicate, surprisingly, that insulin receptor signaling in noncanonical insulin target tissues is sufficient to maintain fuel homeostasis and prevent diabetes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
diabetic ketoacidosis  ISOInsr (Mus musculus)1302526; 1302526 RGD 
diabetic ketoacidosis  IMP 1302526 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Insr  (insulin receptor)

Genes (Mus musculus)
Insr  (insulin receptor)

Genes (Homo sapiens)
INSR  (insulin receptor)


Additional Information