Glycogen synthesis kinase-3β involves in the analgesic effect of liraglutide on diabetic neuropathic pain

被引：5

作者：

Zhang, Yuanpin ^{[1
]}

Zhang, Qi ^{[1
]}

Bai, Yuetian ^{[1
]}

Zheng, Hangping ^{[1
]}

Ji, Lijin ^{[1
]}

Zhu, Xiaoming ^{[1
]}

Sun, Wanwan ^{[1
]}

Liu, Xiaoxia ^{[1
]}

Zhang, Shuo ^{[1
]}

Li, Yiming ^{[1
]}

Lu, Bin ^{[1
,2
]}

机构：

[1] Fudan Univ, Huashan Hosp, Dept Endocrinol & Metab, Shanghai 200040, Peoples R China

[2] 12 Middle Urumqi Rd, Shanghai, Peoples R China

来源：

JOURNAL OF DIABETES AND ITS COMPLICATIONS | 2023年 / 37卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Glycogen synthesis kinase-3; Diabetic neuropathic pain; Liraglutide; NOD-like receptor protein 3 inflammasome; NLRP3; INFLAMMASOME; DORSAL-HORN; ACTIVATION; MECHANISMS; MICROGLIA; INTERLEUKIN-1-BETA; PHYSIOLOGY; MORPHINE; CELLS; RATS;

D O I：

10.1016/j.jdiacomp.2023.108416

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims: Explore whether Glycogen synthesis kinase-3 beta (GSK3 beta) involved in the analgesic effect of liraglutide on diabetic neuropathic pain (DNP).Methods: DNP was induced by streptozocin (STZ) in WT and GSK3 beta(S9A) mice, which carried a constitutively active form of GSK3 beta. DNP mice were intracerebroventricularly injected with liraglutide 5 weeks after STZ in-jection. The behavior of neuropathic pain was evaluated 2 h after drugs administration. The microglial activation and the expression of NOD-like receptor protein 3 (NLRP3) in microglia in cortex were evaluated. The role of GSK3 beta in the inhibitory effect of liraglutide on the NLRP3 inflammasome was explored in BV2 microglia.Results: Intracerebroventricular administration of liraglutide significantly relieved neuropathic pain and inhibited the activation of cortical microglia in WT mice with DNP. But the effect of liraglutide disappeared in GSK3 beta(S9A) mice. In BV2 microglia, GSK3 beta inhibitor significantly suppressed NLRP3 inflammasome activation. And activating GSK3 beta through GSK3 beta(S9A) lentivirus significantly blocked the inhibitory effect of liraglutide on NLRP3 inflammasome in BV2 microglia. Intracerebroventricular administration of liraglutide significantly inhibited the expression of NLRP3 in cortex microglia of DNP group in WT mice but failed in GSK3 beta(S9A) mice. Conclusion: GSK3 beta involves in the analgesic effect of liraglutide on DNP through NLRP3 inflammasome in microglia.

引用

页数：8

共 50 条

[41] INHIBITION OF GLYCOGEN-SYNTHASE KINASE-3 BY POLYCATIONS
HEGAZY, MG
SCHLENDER, KK
WILSON, SE
REIMANN, EM
FASEB JOURNAL, 1988, 2 (04): : A596 - A596
[42] QSAR modeling of the inhibition of Glycogen Synthase Kinase-3
Katritzky, Alan R.
Pacureanu, Liliana M.
Dobchev, Dimitar A.
Fara, Dan C.
Duchowicz, Pablo R.
Karelson, Mati
BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (14) : 4987 - 5002
[43] Glycogen synthase kinase-3 a negative regulator of hypertrophy
Haq, SE
Choukroun, G
Lee, KH
Ranu, H
Vayssier-Taussat, M
Boecker, W
Woodgett, J
Molkentin, JD
Michael, A
Force, T
CIRCULATION, 2000, 102 (18) : 140 - 140
[44] Glycogen synthase kinase-3: A potential target for diabetes
Teli, Divya M.
Gajjar, Anuradha K.
BIOORGANIC & MEDICINAL CHEMISTRY, 2023, 92
[45] Glycogen Synthase Kinase-3β in Ischemic Neuronal Death
Hanumanthappa, Pradeep
Densi, Asha
Krishnamurthy, Rajanikant Golgodu
CURRENT NEUROVASCULAR RESEARCH, 2014, 11 (03) : 271 - 278
[46] Presenilin 1 regulation of glycogen synthase kinase-3β
Vestling, M
Cowburn, RF
Lovestone, S
NEUROBIOLOGY OF AGING, 2002, 23 (01) : S517 - S517
[47] Glycogen synthase kinase-3β, mood stabilizers, and neuroprotection
Li, XH
Bijur, GN
Jope, RS
BIPOLAR DISORDERS, 2002, 4 (02) : 137 - 144
[48] Glycogen Synthase Kinase-3 and Leukemia: Restoring the Balance
Birch, Noah W.
Zeleznik-Le, Nancy J.
CANCER CELL, 2010, 17 (06) : 529 - 531
[49] Regulation of glycogen synthase kinase-3 by hexosamines.
Crook, ED
Singh, L
DIABETES, 1996, 45 : 348 - 348
[50] Hyperactivity: Glycogen synthase kinase-3 as a therapeutic target
Mines, Marjelo A.
EUROPEAN JOURNAL OF PHARMACOLOGY, 2013, 708 (1-3) : 56 - 59

← 1 2 3 4 5 →