PMID- 32588693
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20240329
IS  - 1473-2300 (Electronic)
IS  - 0300-0605 (Print)
IS  - 0300-0605 (Linking)
VI  - 48
IP  - 6
DP  - 2020 Jun
TI  - DPP-4 inhibition resembles exercise in preventing type 2 diabetes development by 
      inhibiting hepatic protein kinase C(epsilon) expression in a mouse model of 
      hyperinsulinemia.
PG  - 300060520934635
LID - 10.1177/0300060520934635 [doi]
LID - 0300060520934635
AB  - OBJECTIVE: Interventions for hyperinsulinemia (HINS), an early indicator of type 
      2 diabetes mellitus (T2DM), can significantly reduce the T2DM risk. This study 
      aims to determine how dipeptidyl peptidase-4 (DPP-4) inhibition prevents HINS 
      progression to T2DM through ameliorating hepatic steatosis. METHODS: KKay mice 
      were used as a HINS model and they underwent exercise or received a DPP-4 
      inhibitor, MK0626. Hepatic steatosis was examined and liver diacylglycerol levels 
      were determined. Human hepatic cells (LO2) were treated with MK0626 or 
      transfected with DPP-4 siRNA. Protein kinase C epsilon isoform (PKCepsilon) and DPP-4 
      expression and insulin receptor substrate 1 (IRS-1) phosphorylation were assessed 
      using immunohistochemistry and western blot. RESULTS: KKay mice developed HINS 
      spontaneously at 7 weeks of age. Similar to exercise, MK0626 ameliorated hepatic 
      steatosis and reduced the liver triglyceride and diacylglycerol content. Both 
      exercise and MK0626 suppressed diacylglycerol-induced PKCepsilon expression and 
      restored insulin signaling, which was shown by tyrosine phosphorylation of IRS-1, 
      in the livers of KKay mice. Additionally, silencing DPP-4 or MK0626 treatment 
      decreased PKCepsilon expression in LO2 cells. CONCLUSIONS: Our data demonstrate that 
      DPP-4 inhibition resembles exercise and effectively delays T2DM onset by 
      suppressing hepatic PKCepsilon expression in the HINS mouse model.
FAU - Li, Yu-Peng
AU  - Li YP
AUID- ORCID: 0000-0002-0994-5575
AD  - Tianjin Medical University Chu Hsien-I Memorial Hospital (Tianjin Medical 
      University Metabolic Diseases Hospital), Tianjin, China. NHC Key Laboratory of 
      Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of 
      Metabolic Diseases.
AD  - Military Postgraduate Medical College, Second Medical Center of PLA General 
      Hospital, Beijing, China.
FAU - Xiao, Jing
AU  - Xiao J
AD  - Military Postgraduate Medical College, Second Medical Center of PLA General 
      Hospital, Beijing, China.
FAU - Liang, Xu
AU  - Liang X
AD  - Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, 
      Tianjin Eye Institute, Tianjin, China; Clinical College of Ophthalmology, Tianjin 
      Medical University, Tianjin, China.
FAU - Pei, Yu
AU  - Pei Y
AD  - Military Postgraduate Medical College, Second Medical Center of PLA General 
      Hospital, Beijing, China.
FAU - Han, Xiao-Fei
AU  - Han XF
AD  - Military Postgraduate Medical College, Second Medical Center of PLA General 
      Hospital, Beijing, China.
FAU - Li, Chen-Xi
AU  - Li CX
AD  - Military Postgraduate Medical College, Second Medical Center of PLA General 
      Hospital, Beijing, China.
FAU - Tian, Hui
AU  - Tian H
AD  - Military Postgraduate Medical College, Second Medical Center of PLA General 
      Hospital, Beijing, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Int Med Res
JT  - The Journal of international medical research
JID - 0346411
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.4.14.5 (Dipeptidyl Peptidase 4)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Type 2
MH  - Dipeptidyl Peptidase 4
MH  - *Hyperinsulinism
MH  - *Insulin Resistance
MH  - Liver
MH  - Mice
MH  - Protein Kinase C
PMC - PMC7323281
OTO - NOTNLM
OT  - DPP-4 inhibitor
OT  - PKCepsilon
OT  - hepatic steatosis
OT  - hyperinsulinemia
OT  - type 2 diabetes
EDAT- 2020/06/27 06:00
MHDA- 2021/05/15 06:00
PMCR- 2020/06/26
CRDT- 2020/06/27 06:00
PHST- 2020/06/27 06:00 [entrez]
PHST- 2020/06/27 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/06/26 00:00 [pmc-release]
AID - 10.1177_0300060520934635 [pii]
AID - 10.1177/0300060520934635 [doi]
PST - ppublish
SO  - J Int Med Res. 2020 Jun;48(6):300060520934635. doi: 10.1177/0300060520934635.