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Lixisenatide, a novel GLP-1 analog, protects against cerebral ischemia/reperfusion injury in diabetic rats.
Naunyn Schmiedebergs Arch Pharmacol · 2018
Last updated 2026-05-28In a study on diabetic rats with induced stroke-like brain injury, the GLP-1 drug lixisenatide improved blood sugar control and reduced brain damage better than the diabetes drug glimepiride. Lixisenatide also improved neurological function and lowered markers of brain inflammation and cell death. Additionally, it helped protect blood vessels by increasing a protective protein and reducing harmful stress signals in the arteries.
AI summary of the abstract below.
| Journal | Naunyn Schmiedebergs Arch Pharmacol, 2018 |
|---|---|
| Citations | 34 |
| Relative citation ratio | 1.70 |
| NIH percentile | 68 |
| Molecules | lixisenatide |
| Conditions studied | Type 2 Diabetes |
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.
Verbatim abstract via PubMed 29671019 ↗
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