{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T19:27:40Z","timestamp":1787254060198,"version":"build-2736575974"},"reference-count":32,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"Royal Adelaide Hospital Florey Fellowship"},{"name":"Australian Medical Research Future Fund"},{"name":"Michell Bequest Foundation"},{"name":"University of Adelaide Research Scholarship"},{"name":"The University of Adelaide Faculty of Health and Medical Sciences Early Development Grant"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>The pharmacological actions of glucose-dependent insulinotropic polypeptide (GIP) in type 2 diabetes (T2D) remain incompletely defined. We evaluated the acute effects of intravenous GIP infusion at a pharmacological dose on glucose homeostasis and cardiovascular responses during hyperglycemia in individuals with T2D. Ten participants, whose T2D was managed by diet and\/or metformin monotherapy (n = 4 men and 6 women; mean \u00b1 SEM age 68.2 \u00b1 3.4 years, BMI 31.7 \u00b1 1.2 kg\/m2, HbA1c 6.9% \u00b1 0.6%), were studied on two occasions in a double-blind, randomized, crossover design. During each study visit, hyperglycemia (\u223c15 mmol\/L) was maintained for 210 min by variable intravenous (IV) glucose infusion, and GIP(1\u201342) (4 pmol\/kg\/min) or 0.9% saline was infused IV. Plasma insulin, C-peptide, glucagon, glucose infusion requirements, mean glucose\/insulin ratio (M\/I ratio; a surrogate for insulin sensitivity), heart rate, and blood pressure were assessed. GIP increased baseline-subtracted insulin and C-peptide responses between 0 and 210 min (mean \u00b1 SEM 8,717 \u00b1 1,827 vs. 3,074 \u00b1 698 mU\/L*min, P = 0.003; and 383.1 \u00b1 58.9 vs. 185.0 \u00b1 35.0 nmol\/L*min, P = 0.0005, respectively) and increased glucose infusion requirements to maintain hyperglycemia (mean \u00b1 SEM 6.1 \u00b1 0.6 vs. 4.9 \u00b1 0.4 mg\/kg\/min; P = 0.02), but attenuated glucagon suppression (P = 0.03) and reduced the M\/I ratio (P &amp;lt; 0.0001). GIP also increased heart rate and reduced systolic and diastolic blood pressures (P &amp;lt; 0.01 each). These findings demonstrate that pharmacological GIP retains substantial biological activity in relatively well-controlled T2D, influencing both glucose metabolism and cardiovascular regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>The clinical success of dual glucagon-like peptide 1\/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists has renewed interest in the pharmacological actions of GIP in type 2 diabetes (T2D), although its metabolic and cardiovascular effects remain incompletely understood. The study evaluated the effects of a pharmacological GIP infusion on glucose homeostasis and cardiovascular responses during hyperglycemia in individuals with T2D. GIP stimulated insulin secretion and increased whole-body glucose disposal during hyperglycemia while modestly attenuating glucagon suppression and impairing insulin sensitivity. GIP also augmented heart rate and reduced blood pressure. Our findings demonstrate that GIP remains biologically active in T2D and pharmacological doses modulate glucose metabolism and cardiovascular function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db26-0267","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:49:33Z","timestamp":1784054973000},"page":"1701-1708","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Pharmacological GIP Infusion on Insulin, Glucagon, and Cardiovascular Responses During Hyperglycemia in Type 2 Diabetes"],"prefix":"10.2337","volume":"75","author":[{"given":"Yixuan","family":"Sun","sequence":"first","affiliation":[{"name":"School of Medicine and Centre of Research in Translating Nutritional Science to Good Health, College of Health, Adelaide University 1 , Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0054-9269","authenticated-orcid":false,"given":"Cong","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Medicine and Centre of Research in Translating Nutritional Science to Good Health, College of Health, Adelaide University 1 , Adelaide, South Australia, Australia"},{"name":"Endocrine and Metabolic Unit, Royal Adelaide Hospital 2 , Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9400-3840","authenticated-orcid":false,"given":"Weikun","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medicine and Centre of Research in Translating Nutritional Science to Good Health, College of Health, Adelaide University 1 , Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Bound","sequence":"additional","affiliation":[{"name":"School of Medicine and Centre of Research in Translating Nutritional Science to Good Health, College of Health, Adelaide University 1 , Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Grivell","sequence":"additional","affiliation":[{"name":"School of Medicine and Centre of Research in Translating Nutritional Science to Good Health, College of Health, Adelaide University 1 , Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1155-5816","authenticated-orcid":false,"given":"Karen L.","family":"Jones","sequence":"additional","affiliation":[{"name":"School of Medicine and Centre of Research in Translating Nutritional Science to Good Health, College of Health, Adelaide University 1 , Adelaide, South Australia, Australia"},{"name":"Endocrine and Metabolic Unit, Royal Adelaide Hospital 2 , Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Horowitz","sequence":"additional","affiliation":[{"name":"School of Medicine and Centre of Research in Translating Nutritional Science to Good Health, College of Health, Adelaide University 1 , Adelaide, South Australia, Australia"},{"name":"Endocrine and Metabolic Unit, Royal Adelaide Hospital 2 , Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A.","family":"Macdonald","sequence":"additional","affiliation":[{"name":"Division of Physiology, Pharmacology and Neuroscience, School of Life Sciences, Queen's Medical Centre 3 , Nottingham, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5527-256X","authenticated-orcid":false,"given":"Christopher 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