{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:42:17Z","timestamp":1791978137427,"version":"4.4.0"},"reference-count":24,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100007028","name":"The Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"crossref","award":["1912-03551"],"award-info":[{"award-number":["1912-03551"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Glucose-dependent insulinotropic polypeptide (GIP[1\u201342]) increases glucagon levels in the presence of normal-to-low plasma glucose concentrations in individuals with type 1 diabetes (T1D), suggesting its potential use as a safeguard against hypoglycemia. We investigated the dose-dependent effects of exogenous full-length GIP[1\u201342] and its truncated variant GIP[1\u201330]NH2 on glucagon concentrations during insulin-induced hypoglycemia in individuals with T1D. In a randomized, double-blind, placebo-controlled, crossover study, 10 men with C-peptide\u2013negative T1D participated in five experimental visits. On each visit, participants received a 135-min intravenous infusion of GIP[1\u201342] or GIP[1\u201330]NH2 (both at 4 or 8 pmol\/kg\/min), or placebo. The infusion period included a 30-min euglycemic period, a 60-min insulin-induced hypoglycemic clamp (target glucose 2.5 mmol\/L), and a 45-min recovery phase. During the euglycemic period, glucagon concentrations were higher with all GIP infusions compared with placebo, reaching statistical significance only for GIP[1\u201330]NH2 (P &amp;lt; 0.05 for both high-dose [8 pmol\/kg\/min] and low-dose [4 pmol\/kg\/min]). However, the insulin infusion suppressed glucagon to similarly low levels for all interventions. Both GIP variants increased norepinephrine levels, and high-dose GIP[1\u201342] slightly reduced the amount of glucose required to recover from hypoglycemia. These findings demonstrate that although GIP acutely increases glucagon concentrations during euglycemia in T1D, insulin infusion overrides this effect, indicating that elevated GIP levels alone cannot effectively restore the glucagon response to insulin-induced hypoglycemia in T1D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>The glucose-dependent glucagonotropic effects of glucose-dependent insulinotropic polypeptide (GIP) variants in type 1 diabetes (T1D) are incompletely understood. We investigated whether native full-length GIP[1\u201342] and its truncated variant GIP[1\u201330]NH2 increase glucagon concentrations during insulin-induced hypoglycemia in individuals with T1D. During euglycemia, both GIP variants increased glucagon [statistically significantly for GIP(1\u201330)NH2 only] and norepinephrine, but insulin suppressed glucagon levels similarly across interventions. High-dose GIP[1\u201342] was associated with slightly reduced glucose requirements during recovery from hypoglycemia, suggestive of increased hepatic glucose production through either glucagon or norepinephrine action.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-1128","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T18:34:57Z","timestamp":1778006097000},"page":"1142-1149","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":1,"title":["The Glucagonotropic Effect of GIP Is Negated During Insulin-Induced Hypoglycemia in Type 1 Diabetes: A Randomized, Placebo-Controlled, Crossover Study"],"prefix":"10.2337","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0764-8452","authenticated-orcid":false,"given":"Nikolaj E.","family":"S\u00f8rum","sequence":"first","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen 1 , Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Warn\u00f8e","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen 1 , Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6853-3805","authenticated-orcid":false,"given":"Jens J.","family":"Holst","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen 2 , Copenhagen, Denmark"},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen 3 , Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8509-2036","authenticated-orcid":false,"given":"Bolette","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen 2 , Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7880-8515","authenticated-orcid":false,"given":"L\u00e6rke S.","family":"Gasbjerg","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen 1 , Copenhagen, Denmark"},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen 3 , Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7529-4264","authenticated-orcid":false,"given":"Joachim","family":"St\u00f8rling","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen 2 , Copenhagen, Denmark"},{"name":"Steno Diabetes Center Copenhagen 4 , Herlev, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne L.","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Vejle Hospital, University Hospital of Southern Denmark 5 , Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0097-7052","authenticated-orcid":false,"given":"Thomas F.","family":"Dejgaard","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nephrology, Nordsj\u00e6llands Hospital Hiller\u00f8d, University of Copenhagen 6 , Hiller\u00f8d, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkel B.","family":"Christensen","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen 1 , Copenhagen, Denmark"},{"name":"Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen 7 , Copenhagen, Denmark"},{"name":"Copenhagen Center for Translational Research, Bispebjerg Hospital, University of Copenhagen 8 , Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen 9 , Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4358-6331","authenticated-orcid":false,"given":"Jonathan E.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Duke Molecular Physiology Institute, Duke University 10 , Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-5034","authenticated-orcid":false,"given":"Filip K.","family":"Knop","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen 1 , Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen 9 , Copenhagen, Denmark"},{"name":"Novo Nordisk A\/S 11 , Bagsv\u00e6rd, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1212-3764","authenticated-orcid":false,"given":"Asger B.","family":"Lund","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen 1 , Copenhagen, Denmark"},{"name":"Steno Diabetes Center Copenhagen 4 , Herlev, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, 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