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Oral and intravenous glucose administration elicit opposing microvascular blood flow responses in skeletal muscle of healthy people : Role of incretins
Roberts-Thomson, Katherine Parker, Lewan Betik, Andrew C. Wadley, Greg D. Della Gatta, Paul A. Marwick, Thomas H. Keske, Michelle A.
Roberts-Thomson, Katherine
Parker, Lewan
Betik, Andrew C.
Wadley, Greg D.
Della Gatta, Paul A.
Marwick, Thomas H.
Keske, Michelle A.
Abstract
Insulin infusion increases skeletal muscle microvascular blood flow (MBF) in healthy people but is impaired during insulin resistance. However, we have shown that eliciting insulin secretion via oral glucose loading in healthy people impairs muscle MBF, whilst others have demonstrated intravenous glucose infusion stimulates MBF. We aimed to show that the route of glucose administration (oral versus intravenous) influences muscle MBF, and explore potential gut-derived hormones that may explain these divergent responses. Ten healthy individuals underwent a 120 min oral glucose tolerance test (OGTT; 75 g glucose) and on a subsequent occasion an intravenous glucose tolerance test (IVGTT, bypassing the gut) matched for similar blood glucose excursions. Femoral artery and thigh muscle microvascular (contrast-enhanced ultrasound) haemodynamics were measured at baseline and during the OGTT/IVGTT. Plasma insulin, C-peptide, glucagon, non-esterified fatty acids and a range of gut-derived hormones and incretins (gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1(GLP-1)) were measured at baseline and throughout the OGTT/IVGTT. The IVGTT increased whereas the OGTT impaired MBF (1.3-fold versus 0.5-fold from baseline, respectively, P = 0.0006). The impairment in MBF during the OGTT occurred despite producing 2.8-fold higher plasma insulin concentrations (P = 0.0001). The change in MBF from baseline (ΔMBF) negatively correlated with ΔGIP concentrations (r = −0.665, P < 0.0001). The natural log ratio of incretins GLP-1:GIP was positively associated with ΔMBF (r = 0.658, P < 0.0001), suggesting they have opposing actions on the microvasculature. Postprandial hyperglycaemia per se does not acutely determine opposing microvascular responses between OGTT and IVGTT. Incretins may play a role in modulating skeletal muscle MBF in humans.
Keywords
cardiovascular physiology, gastrointestinal physiology, hyperglycaemia, insulin, skeletal muscle
Date
2022
Type
Journal article
Journal
The Journal of Physiology
Book
Volume
600
Issue
7
Page Range
1667-1681
Article Number
ACU Department
Collections
Relation URI
DOI
Source URL
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
CC BY 4.0
File Access
Open
Notes
© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.