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Locally delivered GLP-1 analogues liraglutide and exenatide enhance microvascular perfusion in individuals with and without type 2 diabetes
- Source :
- Diabetologia
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- 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
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14320428 and 0012186X
- Volume :
- 62
- Database :
- OpenAIRE
- Journal :
- Diabetologia
- Accession number :
- edsair.doi.dedup.....69777fd043ec4b01f73b1cd9de6f5d8e