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The DPP-4 inhibitor...
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Darsalia, VKarolinska Institutet
(author)
The DPP-4 inhibitor linagliptin counteracts stroke in the normal and diabetic mouse brain: a comparison with glimepiride
- Article/chapterEnglish2013
Publisher, publication year, extent ...
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2013-03-14
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American Diabetes Association,2013
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:126437201
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http://kipublications.ki.se/Default.aspx?queryparsed=id:126437201URI
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https://doi.org/10.2337/db12-0988DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Type 2 diabetes is a strong risk factor for stroke. Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor in clinical use against type 2 diabetes. The aim of this study was to determine the potential antistroke efficacy of linagliptin in type 2 diabetic mice. To understand whether efficacy was mediated by glycemia regulation, a comparison with the sulfonylurea glimepiride was done. To determine whether linagliptin-mediated efficacy was dependent on a diabetic background, experiments in nondiabetic mice were performed. Type 2 diabetes was induced by feeding the mice a high-fat diet for 32 weeks. Mice were treated with linagliptin/glimepiride for 7 weeks. Stroke was induced at 4 weeks into the treatment by transient middle cerebral artery occlusion. Blood DPP-4 activity, glucagon-like peptide-1 (GLP-1) levels, glucose, body weight, and food intake were assessed throughout the experiments. Ischemic brain damage was measured by determining stroke volume and by stereologic quantifications of surviving neurons in the striatum/cortex. We show pronounced antistroke efficacy of linagliptin in type 2 diabetic and normal mice, whereas glimepiride proved efficacious against stroke in normal mice only. These results indicate a linagliptin-mediated neuroprotection that is glucose-independent and likely involves GLP-1. The findings may provide an impetus for the development of DPP-4 inhibitors for the prevention and treatment of stroke in diabetic patients.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Ortsater, HKarolinska Institutet
(author)
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Olverling, AKarolinska Institutet
(author)
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Darlof, E
(author)
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Wolbert, PKarolinska Institutet
(author)
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Nystrom, TKarolinska Institutet
(author)
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Klein, T
(author)
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Sjoholm, A
(author)
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Patrone, CKarolinska Institutet
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:Diabetes: American Diabetes Association62:4, s. 1289-12961939-327X0012-1797
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Diabetes
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