PMID- 24039692
OWN - NLM
STAT- MEDLINE
DCOM- 20140610
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 9
DP  - 2013
TI  - Cdk5 inhibitory peptide (CIP) inhibits Cdk5/p25 activity induced by high glucose 
      in pancreatic beta cells and recovers insulin secretion from p25 damage.
PG  - e63332
LID - 10.1371/journal.pone.0063332 [doi]
LID - e63332
AB  - 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.
FAU - Zheng, Ya-Li
AU  - Zheng YL
AD  - Department of Nephrology, Ningxia People's Hospital, Yinchuan, Ningxia Province, 
      China.
FAU - Li, Congyu
AU  - Li C
FAU - Hu, Ya-Fang
AU  - Hu YF
FAU - Cao, Li
AU  - Cao L
FAU - Wang, Hui
AU  - Wang H
FAU - Li, Bo
AU  - Li B
FAU - Lu, Xiao-Hua
AU  - Lu XH
FAU - Bao, Li
AU  - Bao L
FAU - Luo, Hong-Yan
AU  - Luo HY
FAU - Shukla, Varsha
AU  - Shukla V
FAU - Amin, Niranjana D
AU  - Amin ND
FAU - Pant, Harish C
AU  - Pant HC
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130905
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cdk5 inhibitory peptide, human)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Peptide Fragments)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.22 (Cdk5 protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cyclin-Dependent Kinase 5/*metabolism
MH  - Diabetes Mellitus, Type 2/drug therapy/enzymology
MH  - Enzyme Activation
MH  - Glucose/pharmacology/*physiology
MH  - HEK293 Cells
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/*drug effects/enzymology/metabolism
MH  - Mice
MH  - Nerve Tissue Proteins/*pharmacology
MH  - Peptide Fragments/*pharmacology
MH  - Transcriptional Activation
PMC - PMC3764143
COIS- Competing Interests: The authors have declared the following interests: Congyu Li 
      is employed by Pharmerit North America. There are no patents, products in 
      development or marketed products to declare. This does not alter the authors' 
      adherence to all the PLOS ONE policies on sharing data and materials, as detailed 
      online in the guide for authors.
EDAT- 2013/09/17 06:00
MHDA- 2014/06/11 06:00
PMCR- 2013/09/05
CRDT- 2013/09/17 06:00
PHST- 2013/01/05 00:00 [received]
PHST- 2013/04/02 00:00 [accepted]
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2014/06/11 06:00 [medline]
PHST- 2013/09/05 00:00 [pmc-release]
AID - PONE-D-13-01069 [pii]
AID - 10.1371/journal.pone.0063332 [doi]
PST - epublish
SO  - PLoS One. 2013 Sep 5;8(9):e63332. doi: 10.1371/journal.pone.0063332. eCollection 
      2013.