Linked Life Data

20829391

Source:http://linkedlifedata.com/resource/pubmed/id/20829391

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-9-29
pubmed:abstractText
Impairment of insulin and IGF-I signaling in the brain is one of the causes of dementia associated with diabetes mellitus and Alzheimer's disease. However, the precise pathological processes are largely unknown. In the present study, we found that SH2-containing inositol 5'-phosphatase 2 (SHIP2), a negative regulator of phosphatidylinositol 3,4,5-trisphosphate-mediated signals, is widely expressed in adult mouse brain. When a dominant-negative mutant of SHIP2 was expressed in cultured neurons, insulin signaling was augmented, indicating physiological significance of endogenous SHIP2 in neurons. Interestingly, SHIP2 mRNA and protein expression levels were significantly increased in the brain of type 2 diabetic db/db mice. To investigate the impact of increased expression of SHIP2 in the brain, we further employed transgenic mice overexpressing SHIP2 and found that increased amounts of SHIP2 induced the disruption of insulin/IGF-I signaling through Akt. Neuroprotective effects of insulin and IGF-I were significantly attenuated in cultured cerebellar granule neurons from SHIP2 transgenic mice. Consistently, terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay demonstrated that the number of apoptosis-positive cells was increased in cerebral cortex of the transgenic mice at an elderly age. Furthermore, SHIP2 transgenic mice exhibited impaired memory performance in the Morris water maze, step-through passive avoidance, and novel-object-recognition tests. Importantly, inhibition of SHIP2 ameliorated the impairment of hippocampal synaptic plasticity and memory formation in db/db mice. These results suggest that SHIP2 is a potent negative regulator of insulin/IGF-I actions in the brain, and excess amounts of SHIP2 may be related, at least in part, to brain dysfunction in insulin resistance with type 2 diabetes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1944-9917
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1965-77
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20829391-Aging, pubmed-meshheading:20829391-Animals, pubmed-meshheading:20829391-Brain, pubmed-meshheading:20829391-Cells, Cultured, pubmed-meshheading:20829391-Diabetes Mellitus, Type 2, pubmed-meshheading:20829391-Enzyme Inhibitors, pubmed-meshheading:20829391-Insulin, pubmed-meshheading:20829391-Insulin Resistance, pubmed-meshheading:20829391-Insulin-Like Growth Factor I, pubmed-meshheading:20829391-Memory, pubmed-meshheading:20829391-Memory Disorders, pubmed-meshheading:20829391-Mice, pubmed-meshheading:20829391-Mice, Mutant Strains, pubmed-meshheading:20829391-Mice, Transgenic, pubmed-meshheading:20829391-Neuronal Plasticity, pubmed-meshheading:20829391-Neurons, pubmed-meshheading:20829391-Neuroprotective Agents, pubmed-meshheading:20829391-Phosphoric Monoester Hydrolases, pubmed-meshheading:20829391-Signal Transduction
pubmed:year
2010
pubmed:articleTitle
The inositol phosphatase SHIP2 negatively regulates insulin/IGF-I actions implicated in neuroprotection and memory function in mouse brain.
pubmed:affiliation
Department of Clinical Pharmacology, University of Toyama, Toyama, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't