دورية أكاديمية
DPP-4 Inhibitor and Sulfonylurea Differentially Reverse Type 2 Diabetes–Induced Blood–Brain Barrier Leakage and Normalize Capillary Pericyte Coverage
| العنوان: | DPP-4 Inhibitor and Sulfonylurea Differentially Reverse Type 2 Diabetes–Induced Blood–Brain Barrier Leakage and Normalize Capillary Pericyte Coverage |
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| المؤلفون: | Elabi, Osama F., Karampatsi, Dimitra, Vercalsteren, Ellen, Lietzau, Grazyna, Nyström, Thomas, Klein, Thomas, Darsalia, Vladimer, Patrone, Cesare, Paul, Gesine |
| المصدر: | Diabetes; 72(3), pp 405-414 (2023) ; ISSN: 0012-1797 |
| بيانات النشر: | American Diabetes Association Inc. |
| سنة النشر: | 2023 |
| المجموعة: | Lund University Publications (LUP) |
| مصطلحات موضوعية: | Endocrinology and Diabetes |
| الوصف: | Microvascular pathology in the brain is one of the suggested mechanisms underlying the increased incidence and progression of neurodegenerative diseases in people with type 2 diabetes (T2D). Although accumulating data suggest a neuroprotective effect of antidiabetics, the underlying mechanisms are unclear. Here, we investigated whether two clinically used antidiabetics, the dipeptidyl pep-tidase-4 inhibitor linagliptin and the sulfonylurea glimepiride, which restore T2D-induced brain vascular pathology. Micro-vascular pathology was examined in the striatum of mice fed for 12 months with either normal chow diet or a high-fat diet (HFD) to induce T2D. A subgroup of HFD-fed mice was treated with either linagliptin or glimepiride for 3 months be-fore sacrifice. We demonstrate that T2D caused leakage of the blood–brain barrier (BBB), induced angiogenesis, and reduced pericyte coverage of microvessels. However, linaglip-tin and glimepiride recovered the BBB integrity and restored the pericyte coverage differentially. Linagliptin normalized T2D-induced angiogenesis and restored pericyte coverage. In contrast, glimepiride enhanced T2D-induced angiogenesis and increased pericyte density, resulting in proper vascular coverage. Interestingly, glimepiride reduced microglial acti-vation, increased microglial–vascular interaction, and increased collagen IV density. This study provides evidence that both DPP-4 inhibition and sulfonylurea reverse T2D-induced BBB leakage, which may contribute to antidiabetic neurorestorative effects. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://lup.lub.lu.se/record/62bfa8e7-a20a-4125-ba13-c9ca18b208a5Test; http://dx.doi.org/10.2337/db22-0674Test; scopus:85148677898; pmid:36448982 |
| DOI: | 10.2337/db22-0674 |
| الإتاحة: | https://doi.org/10.2337/db22-0674Test https://lup.lub.lu.se/record/62bfa8e7-a20a-4125-ba13-c9ca18b208a5Test |
| رقم الانضمام: | edsbas.7FC1243C |
| قاعدة البيانات: | BASE |
| DOI: | 10.2337/db22-0674 |
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