title: Improved glucose tolerance and insulin secretion by inhibition of dipeptidyl peptidase IV in mice.
abstract: We explored whether inhibition of the enzyme dipeptidyl peptidase IV (DPP IV) increases endogenous levels of glucagon-like peptide-1 (GLP-1) and improves glucose tolerance and insulin secretion in mice. Glucose (150 mg) was administered through a gastric gavage with or without the inhibitor of dipeptidyl peptidase IV, valine-pyrrolidide (100 micromol/kg), in high-fat fed glucose intolerant or control C57BL/6J mice. The increase in plasma GLP-1 after gastric glucose was potentiated by dipeptidyl peptidase IV inhibition (P<0.05). Valine-pyrrolidide also potentiated the plasma insulin response to gastric glucose and improved the glucose tolerance in both groups of mice (P<0.001). In contrast, valine-pyrrolidide did not affect glucose-stimulated insulin secretion from isolated islets. This suggests that valine-pyrrolidide improves insulin secretion and glucose tolerance through indirect action, probably through augmentation of levels of GLP-1 and other incretin hormones. Therefore, inhibition of dipeptidyl peptidase IV activity is feasible to exploit as a treatment for glucose intolerance and type 2 diabetes.
authors.affiliation: Department of Medicine, Malmö University Hospital, Lund University, S-205 02, Malmö, Sweden. bo.ahren@medforsk.mas.lu.se
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: H
authors.initials: H
authors.lastname: Mårtensson
authors.forename: B
authors.initials: B
authors.lastname: Balkan
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000502:physiology*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000097:blood; D011480:Protease Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D011480:Protease Inhibitors; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D018819:Dipeptidyl Peptidase 4; D005947:Glucose