RGD Reference Report - Enhanced diabetogenic effect of streptozotocin in mice overexpressing UCP-3 in skeletal muscle. - Rat Genome Database

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Enhanced diabetogenic effect of streptozotocin in mice overexpressing UCP-3 in skeletal muscle.

Authors: Wang, S  Cawthorne, MA  Clapham, JC 
Citation: Wang S, etal., Ann N Y Acad Sci. 2002 Jun;967:112-9.
RGD ID: 2313520
Pubmed: PMID:12079841   (View Abstract at PubMed)

Diabetic patients exhibit varying degrees of increased muscle UCP-3 expression in skeletal muscle and, in rodents, the pancreatoxin streptozotocin (STZ) upregulates UCP-3 mRNA in skeletal and cardiac muscles. We have investigated the development of STZ-induced diabetes in transgenic mice overexpressing UCP-3 in skeletal muscle in order to provide further insight on the functional role of muscle UCP-3. UCP-3 transgenic mice treated with STZ (UCP3-STZ) showed a significant increase in blood glucose concentration 3 days after the last dose of STZ with a progressive induction of diabetes, attaining blood glucose concentrations of 24.7 +/- 1.5 mmol/L on day 17. Wild-type mice treated with STZ (WT-STZ) only started to show an increase in blood glucose concentration 6 days after the last dose of STZ and peaked on day 17 at a lower concentration than in the UCP-STZ mice. The pancreatic insulin content of UCP-3 control mice (UCP3-CON) was decreased relative to wild-type control mice (WT-CON), and STZ reduced the total pancreatic insulin content by 72% in WT-STZ mice and by 88% in UCP3-STZ mice. In an insulin tolerance test, blood glucose concentrations declined more in the UCP-3 transgenic mice than in the wild-type mice. Mice overexpressing UCP-3 in skeletal muscle have a lower pancreatic insulin content, but tend to be more insulin-sensitive. These twin actions result in an increased susceptibility to STZ-induced diabetes in UCP-3 transgenic mice.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus susceptibilityIMP 2313520 RGD 
Experimental Diabetes Mellitus susceptibilityISOUCP3 (Homo sapiens)2313520; 2313520 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ucp3  (uncoupling protein 3)

Genes (Mus musculus)
Ucp3  (uncoupling protein 3 (mitochondrial, proton carrier))

Genes (Homo sapiens)
UCP3  (uncoupling protein 3)


Additional Information