RGD Reference Report - Insulin reduces cerebral ischemia/reperfusion injury in the hippocampus of diabetic rats: a role for glycogen synthase kinase-3beta. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Insulin reduces cerebral ischemia/reperfusion injury in the hippocampus of diabetic rats: a role for glycogen synthase kinase-3beta.

Authors: Collino, M  Aragno, M  Castiglia, S  Tomasinelli, C  Thiemermann, C  Boccuzzi, G  Fantozzi, R 
Citation: Collino M, etal., Diabetes. 2009 Jan;58(1):235-42. Epub 2008 Oct 7.
RGD ID: 5508834
Pubmed: PMID:18840784   (View Abstract at PubMed)
PMCID: PMC2606878   (View Article at PubMed Central)
DOI: DOI:10.2337/db08-0691   (Journal Full-text)

OBJECTIVE: There is evidence that insulin reduces brain injury evoked by ischemia/reperfusion (I/R). However, the molecular mechanisms underlying the protective effects of insulin remain unknown. Insulin is a well-known inhibitor of glycogen synthase kinase-3beta (GSK-3beta). Here, we investigate the role of GSK-3beta inhibition on I/R-induced cerebral injury in a rat model of insulinopenic diabetes. RESEARCH DESIGN AND METHODS: Rats with streptozotocin-induced diabetes were subjected to 30-min occlusion of common carotid arteries followed by 1 or 24 h of reperfusion. Insulin (2-12 IU/kg i.v.) or the selective GSK-3beta inhibitor TDZD-8 (0.2-3 mg/kg i.v.) was administered during reperfusion. RESULTS: Insulin or TDZD-8 dramatically reduced infarct volume and levels of S100B protein, a marker of cerebral injury. Both drugs induced phosphorylation of the Ser9 residue, thereby inactivating GSK-3beta in the rat hippocampus. Insulin, but not TDZD-8, lowered blood glucose. The hippocampi of the drug-treated animals displayed reduced oxidative stress at 1 h of reperfusion as shown by the decreased generation of reactive oxygen species and lipid peroxidation. I/R-induced activation of nuclear factor-kappaB was attenuated by both drug treatments. At 24 h of reperfusion, TDZD-8 and insulin significantly reduced plasma levels of tumor necrosis factor-alpha; neutrophil infiltration, measured as myeloperoxidase activity and intercellular-adhesion-molecule-1 expression; and cyclooxygenase-2 and inducible-NO-synthase expression. CONCLUSIONS: Acute administration of insulin or TDZD-8 reduced cerebral I/R injury in diabetic rats. We propose that the inhibitory effect on the activity of GSK-3beta contributes to the protective effect of insulin independently of any effects on blood glucose.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Reperfusion Injury  ISOS100b (Rattus norvegicus)5508834; 5508834 RGD 
Reperfusion Injury  IEP 5508834 RGD 

Objects Annotated

Genes (Rattus norvegicus)
S100b  (S100 calcium binding protein B)

Genes (Mus musculus)
S100b  (S100 protein, beta polypeptide, neural)

Genes (Homo sapiens)
S100B  (S100 calcium binding protein B)


Additional Information