{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:43:17Z","timestamp":1790066597004,"version":"4.0.1"},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>versus<\/jats:italic>\n                      intravenous) influences muscle MBF, and explore potential gut\u2010derived hormones that may explain these divergent responses. Ten healthy individuals underwent a 120\u00a0min oral glucose tolerance test (OGTT; 75\u00a0g 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\u2010enhanced ultrasound) haemodynamics were measured at baseline and during the OGTT\/IVGTT. Plasma insulin, C\u2010peptide, glucagon, non\u2010esterified fatty acids and a range of gut\u2010derived hormones and incretins (gastric inhibitory polypeptide (GIP) and glucagon\u2010like peptide\u20101(GLP\u20101)) were measured at baseline and throughout the OGTT\/IVGTT. The IVGTT increased whereas the OGTT impaired MBF (1.3\u2010fold\n                      <jats:italic>versus<\/jats:italic>\n                      0.5\u2010fold from baseline, respectively,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0006). The impairment in MBF during the OGTT occurred despite producing 2.8\u2010fold higher plasma insulin concentrations (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0001). The change in MBF from baseline (\u0394MBF) negatively correlated with \u0394GIP concentrations (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a0\u22120.665,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001). The natural log ratio of incretins GLP\u20101:GIP was positively associated with \u0394MBF (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a00.658,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001), suggesting they have opposing actions on the microvasculature. Postprandial hyperglycaemia\n                      <jats:italic>per se<\/jats:italic>\n                      does not acutely determine opposing microvascular responses between OGTT and IVGTT. Incretins may play a role in modulating skeletal muscle MBF in humans.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Insulin or mixed nutrient meals stimulate skeletal muscle microvascular blood flow (MBF) to aid in the delivery of nutrients; however, this vascular effect is lost during insulin resistance.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Food\/drinks containing large glucose loads impair MBF in healthy people; however, this impairment is not observed when glucose is infused intravenously (bypassing the gut).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We investigated skeletal muscle MBF responses to a 75\u00a0g oral glucose tolerance test and intravenous glucose infusion and aimed to identify potential gut hormones responsible for glucose\u2010mediated changes in MBF.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Despite similar blood glucose concentrations, orally ingested glucose impaired, whereas intravenously infused glucose augmented, skeletal muscle MBF. The incretin gastric inhibitory polypeptide was negatively associated with MBF, suggestive of an incretin\u2010mediated MBF response to oral glucose ingestion.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This work provides new insight into why diets high in glucose may be detrimental to vascular health and provides new avenues for novel treatment strategies targeting microvascular dysfunction.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp282428","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T12:15:07Z","timestamp":1642594507000},"page":"1667-1681","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Oral and intravenous glucose administration elicit opposing microvascular blood flow responses in skeletal muscle of healthy people: role of incretins"],"prefix":"10.1113","volume":"600","author":[{"given":"Katherine M.","family":"Roberts\u2010Thomson","sequence":"first","affiliation":[{"name":"Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University  Geelong Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5372-1851","authenticated-orcid":false,"given":"Lewan","family":"Parker","sequence":"additional","affiliation":[{"name":"Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University  Geelong Victoria Australia"},{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Betik","sequence":"additional","affiliation":[{"name":"Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University  Geelong Victoria Australia"},{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6617-4359","authenticated-orcid":false,"given":"Glenn D.","family":"Wadley","sequence":"additional","affiliation":[{"name":"Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University  Geelong Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A. Della","family":"Gatta","sequence":"additional","affiliation":[{"name":"Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University  Geelong Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9065-0899","authenticated-orcid":false,"given":"Thomas H.","family":"Marwick","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0950-4972","authenticated-orcid":false,"given":"Michelle A.","family":"Keske","sequence":"additional","affiliation":[{"name":"Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University  Geelong Victoria Australia"},{"name":"Baker Heart and Diabetes Institute  Melbourne Victoria 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