TY - JOUR

T1 - Arterial responses to infusion of glucagon-like peptide-1 in humans

T2 - A randomized trial study

AU - Ghanizada, Hashmat

AU - Christensen, Rune Häckert

AU - Al-Karagholi, Mohammad Al Mahdi

AU - Elbahi, Fatima Azzahra

AU - Coskun, Hande

AU - Ashina, Messoud

N1 - Funding Information: The following authors, Hashmat Ghanizada, Rune Häckert Christensen, Mohammad Al-Mahdi Al-Karagholi, Fatima Azzahra Elbahi, Hande Coskun reports no conflicts of interest. Messoud Ashina (MA) is a consultant/speaker/scientific advisor for AbbVie, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis and Teva. MA is also the primary investigator for ongoing Allergan, Amgen and Lundbeck clinical trials. MA own no stocks or ownership interest in any pharmaceutical companies. MA serves as associate editor of Brain, associate editor of Journal of Headache and Pain and associate editor of Cephalalgia. MA reports research grants from Lundbeck Foundation, Novo Nordisk Foundation, and research grant from Novartis. Funding Information: The study received financial support from Lundbeck Foundation ( R155-2014-171 ). Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022

Y1 - 2022

N2 - Glucagon-like-peptide-1 (GLP-1) is an incretin hormone implicated in several metabolic and neurological disorders. GLP-1 induces vasodilation and increases blood flow in the peripheral circulation. Whether GLP-1 alters cerebral hemodynamics in humans is yet to be elucidated. In a crossover, double-blind, placebo-controlled, and randomized design, 21 healthy volunteers were assigned to receive intravenous GLP-1 infusion (2.5 pmol/kg/min) or placebo over 20 min on two different days separated by at least one week. We used a noninvasive, well-validated transcranial doppler (TCD) and ultrasound dermascan to reveal the effect of GLP-1 on intra- and extracerebral arteries. The mean blood flow velocity in the middle cerebral artery (VMCA), the diameter of the superficial temporal artery (STA) and radial artery (RA), and facial skin blood flow were measured. In addition, we documented headache and its associated symptoms during and after infusion. Twenty participants were included in the final analysis. We found no difference in the VMCA (P = 0.227), diameter of the STA (P = 0.096) and the RA (P = 0.221) and facial blood flow (P = 0.814) after GLP-1 compared to placebo. There were no differences in HR, SAT, EtCO2, or RF (P > 0.05) on the GLP-1 day compared to the placebo day. We found no differences in the incidence of headache after GLP-1 (n = 10) compared to placebo (n = 7) (P = 0.250). GLP-1 infusion did not affect cerebral hemodynamics and induce headache in humans. Further preclinical studies with validated methods are required to determine if intra – and extracerebral vasculature express GLP-1Rs in humans.

AB - Glucagon-like-peptide-1 (GLP-1) is an incretin hormone implicated in several metabolic and neurological disorders. GLP-1 induces vasodilation and increases blood flow in the peripheral circulation. Whether GLP-1 alters cerebral hemodynamics in humans is yet to be elucidated. In a crossover, double-blind, placebo-controlled, and randomized design, 21 healthy volunteers were assigned to receive intravenous GLP-1 infusion (2.5 pmol/kg/min) or placebo over 20 min on two different days separated by at least one week. We used a noninvasive, well-validated transcranial doppler (TCD) and ultrasound dermascan to reveal the effect of GLP-1 on intra- and extracerebral arteries. The mean blood flow velocity in the middle cerebral artery (VMCA), the diameter of the superficial temporal artery (STA) and radial artery (RA), and facial skin blood flow were measured. In addition, we documented headache and its associated symptoms during and after infusion. Twenty participants were included in the final analysis. We found no difference in the VMCA (P = 0.227), diameter of the STA (P = 0.096) and the RA (P = 0.221) and facial blood flow (P = 0.814) after GLP-1 compared to placebo. There were no differences in HR, SAT, EtCO2, or RF (P > 0.05) on the GLP-1 day compared to the placebo day. We found no differences in the incidence of headache after GLP-1 (n = 10) compared to placebo (n = 7) (P = 0.250). GLP-1 infusion did not affect cerebral hemodynamics and induce headache in humans. Further preclinical studies with validated methods are required to determine if intra – and extracerebral vasculature express GLP-1Rs in humans.

KW - Cerebral blood flow

KW - Doppler

KW - Extracranial

KW - Headache

KW - Human model

KW - Intra-extracerebral

KW - Migraine

KW - Neuropeptides

KW - Pain

KW - Vasodilation

U2 - 10.1016/j.peptides.2022.170736

DO - 10.1016/j.peptides.2022.170736

M3 - Journal article

C2 - 35017010

AN - SCOPUS:85122642312

VL - 150

JO - Peptides

JF - Peptides

SN - 0196-9781

M1 - 170736

ER -