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Published in: Diabetologia 8/2011

01-08-2011 | Research Letter

Dipeptidyl peptidase-4 inhibition increases portal concentrations of intact glucagon-like peptide-1 (GLP-1) to a greater extent than peripheral concentrations in anaesthetised pigs

Authors: K. R. Hjøllund, C. F. Deacon, J. J. Holst

Published in: Diabetologia | Issue 8/2011

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Excerpt

To the Editor: The dipeptidyl peptidase (DPP-4) inhibitors widely used for diabetes treatment may be viewed as being surprisingly effective, particularly when compared with the other class of incretin-based therapy, the glucagon-like peptide-1 (GLP-1) analogues (mimetics), because the inhibitors are associated with only modest increases in peripheral intact GLP-1, whereas much higher agonist concentrations can be achieved using the analogues. It has been calculated that only 10–15% of newly secreted GLP-1 reaches the pancreas as the intact hormone via the circulation [1, 2] because of local and hepatic DPP-4-mediated degradation, leading to the suggestion that GLP-1 may act more locally by interacting with afferent neurons within the intestine or portal vein before it is degraded by DPP-4. Thus it could be speculated that local concentrations of intact GLP-1, particularly after administration of DPP-4 inhibitor, may be much higher than peripheral venous concentrations, which could, at least partially, explain the effectiveness of the inhibitors [3]. However, it is at present unknown what the actual concentrations of endogenous GLP-1 are in the various vascular beds and how much intact GLP-1 concentrations in sites such as the portal vein rise following DPP-4 inhibition. …
Appendix
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Literature
1.
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2.
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4.
go back to reference Simonsen L, Pilgaard S, Carr RD, Kanstrup AB, Holst JJ, Deacon CF (2009) Inhibition of neutral endopeptidase 24.11 does not potentiate the improvement in glycemic control obtained with dipeptidyl peptidase-4 inhibition in diabetic Goto–Kakizaki rats. Horm Metab Res 41:851–853PubMedCrossRef Simonsen L, Pilgaard S, Carr RD, Kanstrup AB, Holst JJ, Deacon CF (2009) Inhibition of neutral endopeptidase 24.11 does not potentiate the improvement in glycemic control obtained with dipeptidyl peptidase-4 inhibition in diabetic Goto–Kakizaki rats. Horm Metab Res 41:851–853PubMedCrossRef
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Metadata
Title
Dipeptidyl peptidase-4 inhibition increases portal concentrations of intact glucagon-like peptide-1 (GLP-1) to a greater extent than peripheral concentrations in anaesthetised pigs
Authors
K. R. Hjøllund
C. F. Deacon
J. J. Holst
Publication date
01-08-2011
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 8/2011
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-011-2168-7

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