{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T18:22:30Z","timestamp":1771006950470,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T00:00:00Z","timestamp":1643500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010148523"],"award-info":[{"award-number":["PJT\u2010148523"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aspenjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Parenter Enteral Nutr"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Short bowel syndrome (SBS) is characterized by malabsorption requiring parenteral nutrition. The intestinotrophic glucagon\u2010like peptide (GLP)\u20102 receptor agonist, h[Gly2]GLP2, is used to treat patients with SBS. Evidence suggests that GLP\u20101 receptor agonists\u00a0such as exendin\u20104 (Ex4)\u00a0may be beneficial\u00a0in SBS\u00a0given their ability to increase intestinal growth and delay gastric emptying (GE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Intestinal growth, body weight (BW), food intake (FI), GE, gastrointestinal (GI) transit, intestinal permeability, and glucose tolerance were investigated in male and female C57\/BL6 mice following vehicle, h[Gly2]GLP2, or Ex4 treatment, alone or in combination at \u201clow,\u201d \u201cmedium,\u201d and \u201chigh\u201d doses (0.1, 0.5, 1.0 and 0.01, 0.05, 0.1 \u03bcg\/g, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Only the h[Gly2]GLP2 low\/Ex4 high\u2010dose combination additively increased small intestinal (SI) weight compared with vehicle and both monoagonists (<jats:italic>P<\/jats:italic> &lt; 0.01\u20130.001), via increased villus height (<jats:italic>P<\/jats:italic> &lt; 0.01) and SI length (<jats:italic>P<\/jats:italic> &lt; 0.05). This combination had no effects on BW; FI; and fat, liver, spleen, heart, and kidney weights but reduced GI transit (<jats:italic>P<\/jats:italic> &lt; 0.001) versus low\u2010dose h[Gly2]GLP2 monotreatment and abrogated the inhibitory effects of high\u2010dose Ex4 on GE (<jats:italic>P<\/jats:italic> &lt; 0.01) and of low\u2010dose h[Gly2]GLP2 on intestinal permeability (<jats:italic>P<\/jats:italic> &lt; 0.05). Ex4\u2010induced improvements in glucose homeostasis were maintained upon combination with h[Gly2]GLP2 (<jats:italic>P<\/jats:italic> &lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that combining specific doses of GLP\u20102\u2010 and GLP\u20101 receptor agonists additively improves SI growth and GI transit without detrimental effects on BW, FI, GE, and glucose homeostasis, and may be useful for the treatment of patients with SBS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jpen.2307","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T16:04:07Z","timestamp":1637942647000},"page":"1361-1370","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Complementary and antagonistic effects of combined glucagon\u2010like peptide\u20102 and glucagon\u2010like peptide\u20101 receptor agonist administration on parameters relevant to 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