{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:07:04Z","timestamp":1761919624655},"reference-count":61,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2012,9,17]],"date-time":"2012-09-17T00:00:00Z","timestamp":1347840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Glucagon\u2010like peptide\u20101 (Glp1) regulates hepatic glucose production (HGP) and muscle glucose uptake (MGU) via its ability to stimulate insulin secretion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using exercise as a means to stimulate glucose flux independently of insulin secretion, we observed that Glp1 receptor (Glp1r) knockout (Glp1r<jats:sup>\u2212\/\u2212<\/jats:sup>) mice become hyperglycaemic but display normal rates of MGU.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Since euglycaemia during exercise is typically maintained by matching rates of HGP to rates of MGU, we hypothesize that exercise\u2010induced hyperglycaemia in Glp1r<jats:sup>\u2212\/\u2212<\/jats:sup> mice is due to excessive HGP.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using innovative catheterization and isotope dilution techniques, we demonstrate that hyperglycaemia in exercising Glp1r<jats:sup>\u2212\/\u2212<\/jats:sup> mice is associated with excessive HGP and glucagon secretion.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results suggest an essential and novel role for basal Glp1r signalling in the suppression of alpha cell secretion during exercise.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p><jats:bold>Abstract\u2002<\/jats:bold> In response to oral glucose, glucagon\u2010like peptide\u20101 receptor (Glp1r) knockout (Glp1r<jats:sup>\u2212\/\u2212<\/jats:sup>) mice become hyperglycaemic due to impaired insulin secretion. Exercise also induces hyperglycaemia in Glp1r<jats:sup>\u2212\/\u2212<\/jats:sup> mice. In contrast to oral glucose, exercise decreases insulin secretion. This implies that exercise\u2010induced hyperglycaemia in Glp1r<jats:sup>\u2212\/\u2212<\/jats:sup> mice results from the loss of a non\u2010insulinotropic effect mediated by the Glp1r. Muscle glucose uptake (MGU) is normal in exercising Glp1r<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Thus, we hypothesize that exercise\u2010induced hyperglycaemia in Glp1r<jats:sup>\u2212\/\u2212<\/jats:sup> mice is due to excessive hepatic glucose production (HGP). Wild\u2010type (Glp1r<jats:sup>+\/+<\/jats:sup>) and Glp1r<jats:sup>\u2212\/\u2212<\/jats:sup> mice implanted with venous and arterial catheters underwent treadmill exercise or remained sedentary for 30 min. [3\u2010<jats:sup>3<\/jats:sup>H]glucose was used to estimate rates of glucose appearance (<jats:italic>R<\/jats:italic><jats:sub>a<\/jats:sub>), an index of HGP, and disappearance (<jats:italic>R<\/jats:italic><jats:sub>d<\/jats:sub>). 2[<jats:sup>14<\/jats:sup>C]deoxyglucose was used to assess MGU. Glp1r<jats:sup>\u2212\/\u2212<\/jats:sup> mice displayed exercise\u2010induced hyperglycaemia due to an excessive increase in <jats:italic>R<\/jats:italic><jats:sub>a<\/jats:sub> but normal <jats:italic>R<\/jats:italic><jats:sub>d<\/jats:sub> and MGU. Exercise\u2010induced glucagon levels were \u223c2\u2010fold higher in Glp1r<jats:sup>\u2212\/\u2212<\/jats:sup> mice, resulting in a \u223c2\u2010fold higher glucagon:insulin ratio. Since inhibition of the central Glp1r stimulates HGP, we tested whether intracerebroventricular (ICV) infusion of the Glp1r antagonist exendin(9\u201339) (Ex9) in Glp1r<jats:sup>+\/+<\/jats:sup> mice would result in exercise\u2010induced hyperglycaemia. ICV Ex9 did not enhance glucose levels or HGP during exercise, suggesting that glucoregulatory effects of Glp1 during exercise are mediated via the pancreatic Glp1r. In conclusion, functional disruption of the Glp1r results in exercise\u2010induced hyperglycaemia associated with an excessive increase in glucagon secretion and HGP. These results suggest an essential role for basal Glp1r signalling in the suppression of alpha cell secretion during exercise.<\/jats:p>","DOI":"10.1113\/jphysiol.2012.234914","type":"journal-article","created":{"date-parts":[[2012,8,14]],"date-time":"2012-08-14T03:24:36Z","timestamp":1344914676000},"page":"5245-5255","source":"Crossref","is-referenced-by-count":6,"title":["Regulation of glucose kinetics during exercise by the glucagon\u2010like peptide\u20101 receptor"],"prefix":"10.1113","volume":"590","author":[{"given":"M. A.","family":"Burmeister","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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