Locally delivered GLP-1 analogues liraglutide and exenatide enhance microvascular perfusion in individuals with and without type 2 diabetes
| العنوان: | Locally delivered GLP-1 analogues liraglutide and exenatide enhance microvascular perfusion in individuals with and without type 2 diabetes |
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| المؤلفون: | Kim M. Gooding, Myo Myo Aung, Kate Slade, Leighton A. R. Freeman, Katarina Kos, Jacqueline L. Whatmore, Angela C. Shore |
| المصدر: | Diabetologia |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Glucagon-like peptide-1 analogues, Adult, Male, 0301 basic medicine, Microvascular perfusion, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Type 2 diabetes, Pharmacology, Article, 03 medical and health sciences, 0302 clinical medicine, Glucagon-Like Peptide 1, Enos, Diabetes mellitus, Internal Medicine, medicine, Humans, Obesity, Saline, Aged, Macrovascular disease, Aged, 80 and over, biology, business.industry, Liraglutide, Microcirculation, Hemodynamics, Middle Aged, medicine.disease, biology.organism_classification, 030104 developmental biology, Diabetes Mellitus, Type 2, Linear Models, Exenatide, Female, business, Perfusion, medicine.drug |
| الوصف: | Aims/hypothesis Glucagon-like peptide-1 (GLP-1) analogues reduce the risk of macrovascular disease in diabetes; however, little is known about their microvascular effects. This research examined the microvascular actions of the GLP-1 analogues liraglutide and exenatide in individuals with and without type 2 diabetes (study 1). It also explored the involvement of the GLP-1 receptor (study 2) and the nitric oxide pathway in mediating the microvascular effects of the analogues. Methods Trial design: Studies 1 and 2 had a randomised, controlled, double-blind study design. Study 1 participants, intervention and methods: three participant groups were recruited: individuals with well-controlled type 2 diabetes, and obese and lean individuals without diabetes (21 participants per group). Liraglutide (0.06 mg), exenatide (0.5 μg) and saline (154 mmol/l NaCl; 0.9%) control were microinjected into separate sites in the dermis (forearm) in a randomised order, blinded to operator and participant. Skin microvascular perfusion was assessed by laser Doppler perfusion imaging. Outcomes were stabilised response (mean skin perfusion between 7.5 and 10 min post microinjection) and total response (AUC, normalised for baseline perfusion). Perfusion response to GLP-1 analogues was compared with saline within each group as well as between groups. Study 2 participants, intervention and methods: in healthy individuals (N = 16), liraglutide (0.06 mg) and saline microinjected sites were pretreated with saline or the GLP-1 receptor blocker, exendin-(9,39), in a randomised order, blinded to participant and operator. Outcomes were as above (stabilised response and total perfusion response). Perfusion response to liraglutide was compared between the saline and the exendin-(9,39) pretreated sites. In vitro study: the effects of liraglutide and exenatide on nitrate levels and endothelial nitric oxide synthase phosphorylation (activation) were examined using human microvascular endothelial cells. Results Study 1 results: both analogues increased skin perfusion (stabilised response and total response) in all groups (n = 21 per group, p |
| تدمد: | 1432-0428 0012-186X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::69777fd043ec4b01f73b1cd9de6f5d8eTest https://doi.org/10.1007/s00125-019-4918-xTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....69777fd043ec4b01f73b1cd9de6f5d8e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320428 0012186X |
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