Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/87081
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dc.contributor.authorWu, T.en
dc.contributor.authorMa, J.en
dc.contributor.authorBound, M.en
dc.contributor.authorChecklin, H.en
dc.contributor.authorDeacon, C.en
dc.contributor.authorJones, K.en
dc.contributor.authorHorowitz, M.en
dc.contributor.authorRayner, C.en
dc.date.issued2014en
dc.identifier.citationDiabetes, 2014; 63(8):2776-2787en
dc.identifier.issn0012-1797en
dc.identifier.issn1939-327Xen
dc.identifier.urihttp://hdl.handle.net/2440/87081-
dc.description.abstractThe impact of variations in gastric emptying, which influence the magnitude of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) secretion, on glucose lowering by dipeptidyl peptidase-4 (DPP-4) inhibitors is unclear. We evaluated responses to intraduodenal glucose infusion (60 g over 120 min [i.e., 2 kcal/min], a rate that predominantly stimulates GIP but not GLP-1) after sitagliptin versus control in 12 healthy lean, 12 obese, and 12 type 2 diabetic subjects taking metformin 850 mg b.i.d. versus placebo. As expected, sitagliptin augmented plasma-intact GIP substantially and intact GLP-1 modestly. Sitagliptin attenuated glycemic excursions in healthy lean and obese but not type 2 diabetic subjects, without affecting glucagon or energy intake. In contrast, metformin reduced fasting and glucose-stimulated glycemia, suppressed energy intake, and augmented total and intact GLP-1, total GIP, and glucagon in type 2 diabetic subjects, with no additional glucose lowering when combined with sitagliptin. These observations indicate that in type 2 diabetes, 1) the capacity of endogenous GIP to lower blood glucose is impaired; 2) the effect of DPP-4 inhibition on glycemia is likely to depend on adequate endogenous GLP-1 release, requiring gastric emptying >2 kcal/min; and 3) the action of metformin to lower blood glucose is not predominantly by way of the incretin axis.en
dc.description.statementofresponsibilityTongzhi Wu, Jing Ma, Michelle J. Bound, Helen Checklin, Carolyn F. Deacon, Karen L. Jones, Michael Horowitz and Christopher K. Rayneren
dc.language.isoenen
dc.publisherAmerican Diabetes Associationen
dc.rights© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.en
dc.subjectHumans; Diabetes Mellitus, Type 2; Obesity; Metformin; Triazoles; Pyrazines; Gastric Inhibitory Polypeptide; Glucose; Blood Glucose; Hypoglycemic Agents; Drug Therapy, Combination; Double-Blind Method; Energy Intake; Gastrointestinal Motility; Adult; Male; Glucagon-Like Peptide 1; Incretinsen
dc.titleEffects of sitagliptin on glycemia, incretin hormones, and antropyloroduodenal motility in response to intraduodenal glucose infusion in healthy lean and obese humans and patients with type 2 diabetes treated with or without metforminen
dc.typeJournal articleen
dc.identifier.rmid0030011039en
dc.identifier.doi10.2337/db13-1627en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/627139en
dc.identifier.pubid107861-
pubs.library.collectionMedicine publicationsen
pubs.library.teamDS01en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidWu, T. [0000-0003-1656-9210]en
dc.identifier.orcidJones, K. [0000-0002-1155-5816]en
dc.identifier.orcidHorowitz, M. [0000-0002-0942-0306]en
dc.identifier.orcidRayner, C. [0000-0002-5527-256X]en
Appears in Collections:Medicine publications

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