The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV.
Abstract
The combined actions of glucose-dependent insulinotropic polypeptide (GIP) and truncated glucagon-like peptide-1 (tGLP-1) may fully account for the incretin effect. These hormones are released from the small intestine in response to oral glucose and stimulate insulin release. Recently, evidence has been provided demonstrating the degradation of GIP-(1-42) and GLP-1-(7-36)NH2 by the serum enzyme dipeptidyl peptidase IV (DPP IV) into the biologically inactive products GIP-(3-42) and GLP-1-(9-36)NH2. The objective of the current investigation was to develop a method to monitor the degradation of these hormones in vivo. Synthetic peptides were radiolabeled and purified by HPLC. Subsequent degradation of the peptides under various conditions was then monitored by further HPLC analysis. Incubation of [125I]GIP-(1-42) or [125I]GLP-1-(7-36)NH2 with Wistar rat serum or purified DPP IV resulted in the major N-terminal-truncated products [125I]GIP-(3-42) and [125I]GLP-1-(9-36)NH2. These products were significantly reduced when the specific DPP IV inhibitor diprotin A was included in the incubation mixture and were absent when serum from DPP IV-deficient rats was used. When the labeled peptides were infused into rats at hormone levels within the physiological range, over 50% was metabolized to the truncated forms within 2 min. These products were absent when the tracers were infused into DPP IV-deficient animals. It is concluded that DPP IV may be a primary inactivating enzyme of both GIP and tGLP-1 in vivo. As the N-terminal-truncated products of the DPP IV cleavage may not be distinguished from the biologically active hormone by currently employed assays, reports of circulating hormone levels should be reconsidered. The method described in this manuscript may be useful for investigating the durations of action of GIP and tGLP-1 in normal and pathophysiological conditions.
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In the citing paper
“DPP-4 cleaves GLP-1(7-36) at the 8th position, generating GLP-1(9–36).”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [257]
In the citing paper
“GIP and GLP-1 are both degraded very quickly by dipeptidyl peptidase 4 (DPP4) [57–59], making analogues of these endogenous hormones poor drug candidates.”
From Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes (2024) · cites this paper as [58]
In the citing paper
“Because GLP-1 has a short half-life of approximately 2 minutes, GLP-1 analogues with longer half-lives have been developed and are now widely used for the treatment of type 2 diabetes mellitus and obesity (41–43).”
From The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission (2023) · cites this paper as [41]
Citations
Cites
Glucagon-like peptide-1 7–36: a physiological incretin in man
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Hamster preproglucagon contains the sequence of glucagon and two related peptides
Bell, G. I., Santerre, R. F., & Mullenbach, G. T. (1983) · Nature · doi:10.1038/302716a0 · Cited by 649
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Proline-Dependent Structural and Biological Properties of Peptides and Proteins
Yaron, A., Naider, F. R., & Scharpé, S. (1993) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409239309082572 · Cited by 551
A new dipeptide naphthylamidase hydrolyzing glycyl-prolyl-?-naphthylamide
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Drucker, D. J., & Nauck, M. A. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69705-5 · Cited by 3,896
Biology of Incretins: GLP-1 and GIP
Baggio, L. L., & Drucker, D. J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.054 · Cited by 3,639
The biology of incretin hormones
Drucker, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.004 · Cited by 2,210
Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868
Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans.
Flint, A., Raben, A., Astrup, A., & Holst, J. J. (1998) · Journal of Clinical Investigation · doi:10.1172/jci990 · Cited by 1,402
Metadata
- Authors
- Kieffer, T. J., McIntosh, C. H., & Pederson, R. A.
- Affiliations
- University of British Columbia (CA)
- ORCID
- Kieffer, T J
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1995-08
- Volume
- 136
- Issue
- 8
- Pages
- 3585-3596
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1978953702
- Cited by
- 1,124
- References
- 36
- Citations by year
- 2026: 9 · 2025: 31 · 2024: 30 · 2023: 15 · 2022: 27 · 2021: 36 · 2020: 23 · 2019: 37 · 2018: 25 · 2017: 40 · 2016: 39 · 2015: 54 · 2014: 47 · 2013: 53 · 2012: 61
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Massachusetts General Hospital
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Peptidase Inhibition and Analysis
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, dipeptidyl peptidase IV, hormone degradation, incretin effect, N-terminal truncation, diprotin A, radiolabeled peptides, insulin secretion, circulating hormone levels
- MeSH terms
- Animals, Blood Physiological Phenomena, Glucagon-Like Peptides, Glucagon, Glucose, Peptide Fragments, Peptides, Protein Precursors, Rats, Inbred F344, Rats, Wistar, Dipeptidyl Peptidase 4, Rats, Glucagon-Like Peptide 1
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