GIP and GLP-1: stepsiblings rather than monozygotic twins within the incretin family
Abstract
The importance of the incretin effect for the postprandial augmentation of insulin released has long been recognized (1). However, there has been a long-standing controversy as to the relative importance of the various gastrointestinal hormones in mediating this effect. While earlier studies suggested a contribution of gastrin, secretin, and cholecystokinin (2), it later became obvious that in humans, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are the predominant incretin hormones (1). Which of the two incretins is the most relevant one is still a matter of debate. Gasbjerg et al. (3) performed studies in healthy human subjects receiving oral glucose loads of 75 g in the fasting state on four different days. The known incretin hormones, GIP and GLP-1, which are secreted in response to glucose administration/absorption, were antagonized with the established peptide receptor antagonist exendin(9-39), blocking the stimulation of GLP-1 receptors, or with the novel GIP receptor antagonist, GIP(3-30)amide, a naturally occurring fragment of intact GIP (full sequence 1–42), which has recently been characterized as a specific GIP receptor antagonist for use in human studies (4). A similar GIP receptor antagonist, GIP(7-30)amide, had previously been used in animal studies but had not been validated for human experiments (5). These incretin receptor antagonists were compared with placebo and used alone and in combination. The result was a slig…
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GLP-1 and GIP contribute to meal-stimulated insulin secretion via GLP-1 and GIP receptors located on pancreatic β cells.
“These hormones contribute to meal-stimulated insulin secre tion via GLP-1 and GIP receptors located on the pancreatic β cell (1).”
From Effects of Tirzepatide vs Semaglutide on β-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test (2024) · cites this paper as [1]
Cites
Frias, J. P., Nauck, M. A., Van, J., Kutner, M. E., Cui, X., Benson, C., Urva, S., Gimeno, R. E., Milicevic, Z., Robins, D., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)32260-8 · Cited by 815 · cited 17× · see citing works
“When exogenous GIP and GLP-1(7-36)amide were exogenously administered to achieve close to physiological concentration profiles under “isoglycemic” conditions, where plasma glucose levels were identical to those after oral glucose administration, GIP in addition to intravenous”
BackgroundMethodResultInfluentialSelf-citationNauck, M. A., & Meier, J. J. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(15)00482-9 · Cited by 503 · cited 4× · see citing works
“Blocking incretins altogether, using exendin(9-39) and GIP(3-30)amide in combination, results in a reduction to;33%, which is very well compatible with an incretin effect of;67% determined for a glucose load of 75 g (1,15).”
BackgroundResultInfluentialSelf-citationImpaired regulation of the incretin effect in patients with type 2 diabetes
Bagger, J. I., Knop, F. K., Lund, A., Vestergaard, H., Holst, J. J., & Vilsbøll, T. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2435 · Cited by 219 · see citing works
Gasbjerg, L. S., Helsted, M. M., Hartmann, B., Jensen, M. H., Gabe, M. B. N., Sparre-Ulrich, A. H., Veedfald, S., Stensen, S., Lanng, A. R., Bergmann, N. C., et al. (2019) · Diabetes · doi:10.2337/db18-1123 · Cited by 193 · see citing works
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GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice
Samms, R. J., Christe, M. E., Collins, K. A. L., Pirro, V., Droz, B. A., Holland, A. K., Friedrich, J. L., Wojnicki, S., Konkol, D. L., Cosgrove, R., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci146353 · Cited by 256 · see citing works
GIP as a Therapeutic Target in Diabetes and Obesity: Insight From Incretin Co-agonists
Holst, J. J., & Rosenkilde, M. M. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa327 · Cited by 207 · see citing works
The intestine as an endocrine organ and the role of gut hormones in metabolic regulation
Bany Bakar, R., Reimann, F., & Gribble, F. M. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00830-y · Cited by 144 · see citing works
GLP-1 agonist to treat obesity and prevent cardiovascular disease: what have we achieved so far
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GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells
Shilleh, A. H., Viloria, K., Broichhagen, J., Campbell, J. E., & Hodson, D. J. (2024) · Peptides · doi:10.1016/j.peptides.2024.171179 · Cited by 39 · see citing works
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- Authors
- Nauck, M. A., & Meier, J. J.
- Affiliations
- St. Josef-Hospital (DE)
- Corresponding author
- Meier, Juris J.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2019-04-16
- Volume
- 68
- Issue
- 5
- Pages
- 897-900
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2936477874
- Cited by
- 65
- References
- 4
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 14 · 2023: 9 · 2022: 8 · 2021: 8 · 2020: 6 · 2019: 2
- FWCI
- 4.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, incretin effect, exendin-9-39, postprandial insulin secretion, oral glucose tolerance, glycemic response, GIP receptor
- MeSH terms
- Gastric Inhibitory Polypeptide, Glucose, Humans, Twins, Monozygotic, Glucagon-Like Peptide 1, Incretins
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