PMID- 29671019
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20181126
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 391
IP  - 7
DP  - 2018 Jul
TI  - Lixisenatide, a novel GLP-1 analog, protects against cerebral 
      ischemia/reperfusion injury in diabetic rats.
PG  - 705-717
LID - 10.1007/s00210-018-1497-1 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is a major risk factor for ischemic stroke 
      accompanied by vascular dysfunction and poor cerebrovascular outcome. 
      Lixisenatide is a glucagon like peptide-1 (GLP-1) analog that is recently used 
      for T2DM treatment with established neuroprotective properties. This study 
      investigated and compared the neuroprotective effect of lixisenatide against 
      glimepiride on diabetic rats subjected to global cerebral ischemia/reperfusion 
      (I/R) injury. T2DM-induced adult male Wistar rats were administered lixisenatide 
      or glimepiride prior to induction of global cerebral I/R-induced injury. Results 
      showed a disturbance in oxidative stress parameters (catalase, reduced 
      glutathione, and malondialdehyde) along with increasing in caspase-3 and tumor 
      necrosis factor-alpha protein expressions in ischemic diabetic brain tissues. An 
      upregulation of protein level of inducible nitric oxide (iNOS) synthase and 
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit, NOX2 gene 
      expression associated with significant suppression of endothelial nitric oxide 
      synthase (eNOS) protein expression are recorded in carotid arteries of diabetic 
      I/R-injured rats. Apart from ameliorating glucose intolerance and insulin 
      resistance, lixisenatide was found to be superior to glimepiride as protective 
      treatment in terms of enhancing behavioral/neurological functions and suppressing 
      cerebral oxidative stress, inflammation, and apoptosis in cerebral I/R-injured 
      diabetic rats. Unlike glimepiride, lixisenatide relieved carotid endothelial 
      dysfunction by increasing eNOS expression. It also dampened vascular 
      nitrosative/oxidative stress via suppression of iNOS and NADPH oxidase 
      expressions. This study supposed that lixisenatide represents a more suitable 
      anti-diabetic therapy for patients who are at risk of ischemic stroke, and even 
      so, the mechanisms of lixisenatide-mediated vascular protection warrant further 
      experimental and clinical investigations.
FAU - Abdel-Latif, Rania G
AU  - Abdel-Latif RG
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, 
      El-Minia, 61111, Egypt.
FAU - Heeba, Gehan H
AU  - Heeba GH
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, 
      El-Minia, 61111, Egypt. gehan_heeba@mu.edu.eg.
FAU - Taye, Ashraf
AU  - Taye A
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, 
      El-Minia, 61111, Egypt.
FAU - Khalifa, Mohamed M A
AU  - Khalifa MMA
AD  - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, 
      El-Minia, 61111, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20180418
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peptides)
RN  - 74O62BB01U (lixisenatide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 1.6.3.- (Cybb protein, rat)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/*drug therapy/metabolism/pathology
MH  - Carotid Arteries/drug effects/metabolism
MH  - Diabetes Mellitus, Experimental/*drug therapy/metabolism
MH  - Glucagon-Like Peptide 1/analogs & derivatives
MH  - Hypoglycemic Agents/pharmacology/*therapeutic use
MH  - Insulin Resistance
MH  - Male
MH  - NADPH Oxidase 2/metabolism
MH  - NADPH Oxidases/metabolism
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Oxidative Stress/drug effects
MH  - Peptides/pharmacology/*therapeutic use
MH  - Rats, Wistar
MH  - Reperfusion Injury/*drug therapy/metabolism/pathology
OTO - NOTNLM
OT  - Cerebral ischemia/reperfusion
OT  - GLP-1
OT  - Glimepiride
OT  - Lixisenatide
OT  - Type 2 diabetes mellitus
OT  - Vascular injury
EDAT- 2018/04/20 06:00
MHDA- 2018/11/27 06:00
CRDT- 2018/04/20 06:00
PHST- 2018/01/10 00:00 [received]
PHST- 2018/04/05 00:00 [accepted]
PHST- 2018/04/20 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2018/04/20 06:00 [entrez]
AID - 10.1007/s00210-018-1497-1 [pii]
AID - 10.1007/s00210-018-1497-1 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2018 Jul;391(7):705-717. doi: 
      10.1007/s00210-018-1497-1. Epub 2018 Apr 18.