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Lixisenatide, a novel GLP-1 analog, protects against cerebral ischemia/reperfusion injury in diabetic rats.
Naunyn Schmiedebergs Arch Pharmacol. 2018 07; 391(7):705-717.NS

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, 61111, Egypt.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, 61111, Egypt. gehan_heeba@mu.edu.eg.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, 61111, Egypt.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, 61111, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29671019

Citation

Abdel-Latif, Rania G., et al. "Lixisenatide, a Novel GLP-1 Analog, Protects Against Cerebral Ischemia/reperfusion Injury in Diabetic Rats." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 391, no. 7, 2018, pp. 705-717.
Abdel-Latif RG, Heeba GH, Taye A, et al. Lixisenatide, a novel GLP-1 analog, protects against cerebral ischemia/reperfusion injury in diabetic rats. Naunyn Schmiedebergs Arch Pharmacol. 2018;391(7):705-717.
Abdel-Latif, R. G., Heeba, G. H., Taye, A., & Khalifa, M. M. A. (2018). Lixisenatide, a novel GLP-1 analog, protects against cerebral ischemia/reperfusion injury in diabetic rats. Naunyn-Schmiedeberg's Archives of Pharmacology, 391(7), 705-717. https://doi.org/10.1007/s00210-018-1497-1
Abdel-Latif RG, et al. Lixisenatide, a Novel GLP-1 Analog, Protects Against Cerebral Ischemia/reperfusion Injury in Diabetic Rats. Naunyn Schmiedebergs Arch Pharmacol. 2018;391(7):705-717. PubMed PMID: 29671019.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lixisenatide, a novel GLP-1 analog, protects against cerebral ischemia/reperfusion injury in diabetic rats. AU - Abdel-Latif,Rania G, AU - Heeba,Gehan H, AU - Taye,Ashraf, AU - Khalifa,Mohamed M A, Y1 - 2018/04/18/ PY - 2018/01/10/received PY - 2018/04/05/accepted PY - 2018/4/20/pubmed PY - 2018/11/27/medline PY - 2018/4/20/entrez KW - Cerebral ischemia/reperfusion KW - GLP-1 KW - Glimepiride KW - Lixisenatide KW - Type 2 diabetes mellitus KW - Vascular injury SP - 705 EP - 717 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch. Pharmacol. VL - 391 IS - 7 N2 - 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. SN - 1432-1912 UR - https://www.unboundmedicine.com/medline/citation/29671019/Lixisenatide_a_novel_GLP_1_analog_protects_against_cerebral_ischemia/reperfusion_injury_in_diabetic_rats_ L2 - https://dx.doi.org/10.1007/s00210-018-1497-1 DB - PRIME DP - Unbound Medicine ER -