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The DPP-4 inhibitor linagliptin counteracts stroke in the normal and diabetic mouse brain: a comparison with glimepiride
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- Darsalia, V (author)
- Karolinska Institutet
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- Ortsater, H (author)
- Karolinska Institutet
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- Olverling, A (author)
- Karolinska Institutet
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- Darlof, E (author)
- Klein, T (author)
- Sjoholm, A (author)
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- (creator_code:org_t)
- 2013-03-14
- 2013
- English.
- In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:4, s. 1289-1296
- Journal article (peer-reviewed)
Abstract
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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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
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- Darsalia, V
- Ortsater, H
- Olverling, A
- Darlof, E
- Wolbert, P
- Nystrom, T
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- Klein, T
- Sjoholm, A
- Patrone, C
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