The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
The Cephalic Insulin Response to Meal Ingestion in Humans Is Dependent on Both Cholinergic and Noncholinergic Mechanisms and Is Important for Postprandial Glycemia
Open accessAbstract
We studied the mechanisms and physiological relevance of the cephalic insulin response to meal ingestion in 12 healthy women (age 63 ± 0.4 years; BMI 27.7 ± 1.7 kg/m2). The ganglionic antagonist, trimethaphan, which impairs neurotransmission across parasympathetic and sympathetic autonomic ganglia, or atropine or saline was given intravenously during the first 15 min after ingestion of a standard meal (350 kcal). During saline infusion, insulin levels increased during the first 10 min after meal ingestion, whereas the first increase in glucose was evident at 15 min. The preabsorptive 10-min insulin response was reduced by 73 ± 11% by trimethaphan (P = 0.009), accompanied by impaired reduction of glucose levels from 25 to 60 min after meal ingestion (Δglucose = –1.27 ± 0.5 [with saline] vs. 0.1 ± 0.4 mmol/l [with trimethaphan]; P = 0.008). This reduction at 25–60 min in glucose levels correlated significantly to the 10-min insulin response (r = 0.65, P = 0.024). The 10-min insulin response to meal ingestion was also reduced by atropine, but only by 20 ± 9% (P = 0.045), which was lower than the reduction with trimethaphan (P = 0.004). The preabsorptive insulin response was not accompanied by any increase in circulating levels of gastric inhibitory polypeptide (GIP) or glucagon-like peptide 1 (GLP-1). In conclusion, 1) the early preabsorptive insulin response to meal ingestion in humans can be largely attributed to autonomic activation mediated by noncholinergic and cholinergic mechanisms, 2) this cephalic insulin response is required for a normal postprandial glucose tolerance, and 3) GIP and GLP-1 do not contribute to the preabsorptive cephalic phase insulin response to meal ingestion.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“The neural mechanism underlying cephalic phase insulin response was found to include cholinergic and non-cholinergic processes136 as well as the dorsal vagal complex located in the medulla oblongata.137”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [136]
The cited source says what the claim attributes to it.
In the citing paper
“Moreover, cephalic phase insulin response is pivotal for ensuring normal postprandial glucose management.136”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [136]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Pharmacological Basis of Therapeutics
(1976) · American Journal of Health-System Pharmacy · doi:10.1093/ajhp/33.4.373a · Cited by 9,216
The pharmacological basis of therapeutics
Starr, I. (1941) · American Heart Journal · doi:10.1016/s0002-8703(41)90958-4 · Cited by 1,907
Kieffer, T. J., & Habener, J. F. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.6.0385 · Cited by 1,062
Autonomic regulation of islet hormone secretion - Implications for health and disease
Åhrén, B. (2000) · Diabetologia · doi:10.1007/s001250051322 · Cited by 929
Tissue and Plasma Concentrations of Amidated and Glycine-Extended Glucagon-Like Peptide I in Humans
Ørskov, C., Rabenhøj, L., Wettergren, A., Kofod, H., & Holst, J. J. (1994) · Diabetes · doi:10.2337/diab.43.4.535 · Cited by 916
Self-citationScrocchi, L. A., Brown, T. J., Maclusky, N., Brubaker, P. L., Auerbach, A. B., Joyner, A. L., & Drucker, D. J. (1996) · Nature Medicine · doi:10.1038/nm1196-1254 · Cited by 793
Mitrakou, A., Kelley, D., Mokan, M., Veneman, T., Pangburn, T., Reilly, J., & Gerich, J. (1992) · New England Journal of Medicine · doi:10.1056/nejm199201023260104 · Cited by 595
Miyawaki, K., Yamada, Y., Yano, H., Niwa, H., Ban, N., Ihara, Y., Kubota, A., Fujimoto, S., Kajikawa, M., Kuroe, A., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.14843 · Cited by 454
Avignon, A., Radauceanu, A., & Monnier, L. (1997) · Diabetes Care · doi:10.2337/diacare.20.12.1822 · Cited by 363
Cephalic phase, reflex insulin secretion neuroanatomical and physiological characterization
Berthoud, H. R., Bereiter, D. A., Trimble, E. R., Siegel, E. G., & Jeanrenaud, B. (1981) · Diabetologia · doi:10.1007/bf00254508 · Cited by 231
van der Hoorn, F. A. J., Boomsma, F., VELD, A. J. M. I., & Schalekamp, M. A. D. H. (1989) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)83003-0 · Cited by 224
Havel, P., & Taborsky, G. (1989) · Endocrine reviews · doi:10.1210/edrv-10-3-332 · Cited by 208
Jamen, F., Persson, K., Bertrand, G., Rodríguez‐Henche, N., Puech, R., Bockaert, J., Åhrén, B., & Brabet, P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9387 · Cited by 190
Nutritional implications of the cephalic-phase reflexes: endocrine responses
Teff, K. L. (2000) · Appetite · doi:10.1006/appe.1999.0282 · Cited by 178
Bruttomesso, D., Pianta, A., Mari, A., Valerio, A., Marescotti, M. C., Avogaro, A., Tiengo, A., & Prato, S. D. (1999) · Diabetes · doi:10.2337/diabetes.48.1.99 · Cited by 166
Calles-Escandon, J., & Robbins, D. C. (1987) · Diabetes · doi:10.2337/diab.36.10.1167 · Cited by 154
Krarup, T., Madsbad, S., Moody, A. J., Regeur, L., FABER, O. K., Holst, J. J., & Sestoft, L. (1983) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-56-6-1306 · Cited by 150
Self-citationBalks, H. J., Holst, J. J., Mühlen, A. V. Z., & Brabant, G. E. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.3.3816 · Cited by 147
Self-citationPagliassotti, M. J., Holste, L. C., Moore, M. C., Neal, D. W., & Cherrington, A. D. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118410 · Cited by 141
Teff, K. L., & Engelman, K. (1996) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1996.270.6.r1371 · Cited by 130
Cephalic phase insulin release in normal weight males: verification and reliability.
Teff, K., Mattes, R., & Engelman, K. (1991) · American Journal of Physiology · doi:10.1152/ajpendo.1991.261.4.e430 · Cited by 127
Mitsui, A., Nohta, H., & Ohkura, Y. (1985) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)82007-1 · Cited by 120
Cephalic phase metabolic responses in normal weight adults
Bruce, D. G., Storlien, L. H., Furler, S. M., & Chisholm, D. J. (1987) · Metabolism · doi:10.1016/0026-0495(87)90106-5 · Cited by 114
Krarup, T., & Holst, J. J. (1984) · Regulatory Peptides · doi:10.1016/0167-0115(84)90005-3 · Cited by 109
Self-citationCephalic Phase of Insulin Secretion in Obese Adolescents
Parra-Covarrubias, A., Rivera-Rodriguez, I., & Almaraz-Ugalde, A. (1971) · Diabetes · doi:10.2337/diab.20.12.800 · Cited by 102
Filipsson, K., Tornøe, K., Holst, J., & Ahrén, B. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.9.4230 · Cited by 91
Self-citationHavel, P. J., & Åhrén, B. (1997) · Diabetes · doi:10.2337/diab.46.5.801 · Cited by 91
Persson, K., Gingerich, R. L., Nayak, S., Wada, K., Wada, E., & Åhrén, B. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.279.5.e956 · Cited by 77
Balks, H. J. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.3.786 · Cited by 71
Early phase insulin infusion and muscarinic blockade in obese and lean subjects
Teff, K. L., & Townsend, R. R. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.1.r198 · Cited by 68
Cephalic-phase insulin in obese and normal-weight men: Relation to postprandial insulin
Teff, K. L., Mattes, R. D., Engelman, K., & Mattern, J. (1993) · Metabolism · doi:10.1016/0026-0495(93)90157-j · Cited by 68
Plasma Insulin Levels During Imaginary Food Ingestion Under Hypnosis
Goldfine, I. D., Abraira, C., Gruenewald, D. A., & Goldstein, M. (1970) · Experimental Biology and Medicine · doi:10.3181/00379727-133-34454 · Cited by 68
Cephalic phase of insulin secretion and food stimulation in humans: a new perspective
Bellisle, F., Louis-Sylvestre, J., Demozay, F., Blazy, D., & Le Magnen, J. (1985) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1985.249.6.e639 · Cited by 67
VIP and PHI in the pig pancreas: coexistence, corelease, and cooperative effects
Holst, J. J., Fahrenkrug, J., Knuhtsen, S., Jensen, S. L., Nielsen, O. V., Lundberg, J. M., & Hökfelt, T. G. M. (1987) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1987.252.2.g182 · Cited by 67
Self-citationÅhrén, B., & Pacini, G. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.4.e701 · Cited by 66
Muscarinic blockade inhibits gastric emptying of mixed-nutrient meal: effects of weight and gender
Teff, K. L., Alavi, A. A., Chen, J., Pourdehnad, M., & Townsend, R. R. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.3.r707 · Cited by 55
Steffens, A. B., van der Gugten, J., Gödeke, J., Luiten, P. G. M., & Strubbe, J. H. (1986) · Physiology & Behavior · doi:10.1016/0031-9384(86)90393-8 · Cited by 52
Gastrin-Releasing Peptide in the Porcine Pancreas
Knuhtsen, S., Holst, J. J., Baldissera, F. G. A., Skak‐Nielsen, T., Poulsen, S. S., Jensen, S. L., & Nielsen, O. V. (1987) · Gastroenterology · doi:10.1016/s0016-5085(87)91071-7 · Cited by 50
Self-citationLarsson, H. E., Åhrén, B., Lindgärde, F., & Berglund, G. (1995) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.1995.tb00882.x · Cited by 45
Tornøe, K., Hannibal, J., Fahrenkrug, J., & Holst, J. J. (1997) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1997.273.2.g436 · Cited by 45
Self-citationCalles-Escandón, J., & Robbins, D. C. (1987) · Diabetes · doi:10.2337/diabetes.36.10.1167 · Cited by 42
Spontaneous insulin fluctuations and the preabsorptive insulin response to food ingestion in humans
Lucas, F., Bellisle, F., & Maio, A. D. (1987) · Physiology & Behavior · doi:10.1016/0031-9384(87)90109-0 · Cited by 41
Direct muscarinic cholinergic inhibition of hepatic glucose production in humans.
Boyle, P. J., Liggett, S. B., SHAH, S. D., & Cryer, P. E. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113617 · Cited by 36
Hormonal control of postprandial thermogenesis in dogs
Diamond, P., & LEBLANC, J. (1987) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1987.253.5.e521 · Cited by 34
PACAP contributes to insulin secretion after gastric glucose gavage in mice
Filipsson, K., Holst, J. J., & Åhrén, B. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.279.2.r424 · Cited by 32
Self-citationMeal-induced insulin secretion in dogs is mediated by both branches of the autonomic nervous system
Benthem, L., Mundinger, T. O., & Taborsky, G. J. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.278.4.e603 · Cited by 28
Morgan, L. (1998) · Biochemical Society Transactions · doi:10.1042/bst0260216 · Cited by 25
Havel, P. J., & Åhrén, B. (1997) · Diabetes · doi:10.2337/diabetes.46.5.801 · Cited by 20
Kohnert, К.-D., Axcrona, U., Hehmke, B., Klöting, I., Sundler, F., & Åhrén, B. (1999) · Regulatory Peptides · doi:10.1016/s0167-0115(99)00044-0 · Cited by 18
Katschinski, M., STEINICKE, C., Reinshagen, M., Dahmen, G., Beglinger, C., Arnold, R., & Adler, G. (1995) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1995.tb01535.x · Cited by 17
SCHNEEBERGER, D., Tappy, L., Temler, E., & Jéquier, E. (1991) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1991.tb01417.x · Cited by 14
Bo, A.-R., Sauerberg, P., & Thomsen, C. (1999) · American Journal of Physiology · doi:10.1152/ajpendo.1999.277.1.e93 · Cited by 11
Electrochemical measurement of neurohypophyseal peptides in hypothalamic and pituitary tissues
Johnson, J., Bennett, G. W., Marsden, C. A., Gardiner, S. M., & Bennett, T. M. (1984) · Regulatory Peptides · doi:10.1016/0167-0115(84)90116-2 · Cited by 4
Cited by
Sorted by citations
The Physiology of Glucagon-like Peptide 1
Holst, J. J. (2007) · Physiological Reviews · doi:10.1152/physrev.00034.2006 · Cited by 3,371
“The response is noticeable after 10 min, but occurs later than the “cephalic phase” stimulation of insulin secretion (3), suggesting that the neuronal, possibly vagal, signals that cause insulin secretion do not influence GLP-1 (or GIP) secretion.”
BackgroundSelf-citationAcetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome
Perry, R. J., Peng, L., Barry, N. A., Cline, G. W., Zhang, D., Cardone, R. L., Petersen, K. F., Kibbey, R. G., Goodman, A. L., & Shulman, G. I. (2016) · Nature · doi:10.1038/nature18309 · Cited by 1,299
Pancreatic regulation of glucose homeostasis.
Röder, P. V., Wu, B., Liu, Y., & Han, W. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.6 · Cited by 985
Animal models of obesity and diabetes mellitus
Kleinert, M., Clemmensen, C., Hofmann, S. M., Moore, M. C., Renner, S., Woods, S. C., Huypens, P., Beckers, J., de Angelis, M. H., Schürmann, A., et al. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.161 · Cited by 893
Obstructive Sleep Apnea and Diabetes
Reutrakul, S., & Mokhlesi, B. (2017) · Chest · doi:10.1016/j.chest.2017.05.009 · Cited by 667
Metadata
- Authors
- Ahrén, B., & Holst, J. J.
- Affiliations
- Department of Medicine, Lund University, Lund, Sweden, and
- University of Copenhagen (DK)
- ORCID
- Holst, Jens J.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2001-05-01
- Volume
- 50
- Issue
- 5
- Pages
- 1030-1038
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2168149788
- Cited by
- 292
- References
- 52
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 11 · 2023: 9 · 2022: 9 · 2021: 15 · 2020: 12 · 2019: 14 · 2018: 17 · 2017: 13 · 2016: 16 · 2015: 22 · 2014: 14 · 2013: 9 · 2012: 11
- FWCI
- 8.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- meal ingestion, postprandial blood glucose, cholinergic mechanisms, trimethaphan, atropine, autonomic nervous system, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, glucose tolerance
- MeSH terms
- Insulin Secretion, Blood Glucose, Blood Pressure, Eating, Female, Ganglionic Blockers, Gastric Inhibitory Polypeptide, Glucagon, Humans, Insulin, Middle Aged, Peptide Fragments, Protein Precursors, Reference Values, Time Factors, Trimethaphan, Body Mass Index, Postmenopause, Postprandial Period, Area Under Curve, Glucagon-Like Peptide 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review