详细记录  
题名:Cdk5 Inhibitory Peptide (CIP) Inhibits Cdk5/p25 Activity Induced by High Glucose in Pancreatic Beta Cells and Recovers Insulin Secretion from p25 Damage.
作者:ZHENG YL; LI C; HU YF; CAO L; WANG H; LI B; LU XH; BAO L; LUO HY; SHUKLA V; AMIN ND; PANT HC;
来源:PLoS One. 2013 Sep 5;8(9):e63332. doi: 10.1371/journal.pone.0063332. [ IF= 3.73 ] ]
URL :10.1371/journal.pone.0063332
日期:20131002
摘要:Cdk5/p25 hyperactivity has been demonstrated to lead to neuron apoptosis and
degenerations. Chronic exposure to high glucose (HG) results in hyperactivity of
Cdk5 and reduced insulin secretion. Here, we set out to determine whether
abnormal upregulation of Cdk5/p25 activity may be induced in a pancreatic beta
cell line, Min6 cells. We first confirmed that p25 were induced in overexpressed
p35 cells treated with HG and increased time course dependence. Next, we showed
that no p25 was detected under short time HG stimulation (4-12 hrs), however was
detectable in the long exposure in HG cells (24 hrs and 48 hrs). Cdk5 activity in
the above cells was much higher than low glucose treated cells and resulted in
more than 50% inhibition of insulin secretion. We confirmed these results by
overexpression of p25 in Min6 cells. As in cortical neurons, CIP, a small
peptide, inhibited Cdk5/p25 activity and restored insulin secretion. The same
results were detected in co-infection of dominant negative Cdk5 (DNCdk5) with
p25. CIP also reduced beta cells apoptosis induced by Cdk5/p25. These studies
indicate that Cdk5/p25 hyperactivation deregulates insulin secretion and induces
cell death in pancreatic beta cells and suggests that CIP may serve as a
therapeutic agent for type 2 diabetes.

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