Regulation of Islet Hormone Release and Gastric Emptying by Endogenous Glucagon-Like Peptide 1 after Glucose Ingestion
Open accessAbstract
Background: Exogenous administration of glucagon-like peptide (GLP)-1 improves glucose tolerance by stimulation of insulin secretion, inhibition of glucagon secretion, and delay of gastric emptying. It is not known which of these effects is involved in the action of endogenous GLP-1 to control blood glucose. To determine the role of endogenous GLP-1 on islet cell function and gastric emptying independent of variable glycemia, we clamped blood glucose before and during glucose ingestion with and without GLP-1 receptor blockade with exendin-[9–39] (Ex-9). Methods: There were 10 healthy subjects that participated in two experiments each, one a control and one with infusion of 750 pm/kg · min Ex-9. Subjects consumed 75 g oral glucose solution mixed with d-xylose and 13C-glucose while their blood glucose levels were held fixed at approximately 8.9 mmol/liter. Results: Plasma insulin levels during hyperglycemia alone were similar in the two studies (control, 282.5 ± 42 vs. Ex-9, 263.8 ± 59 pmol/liter) but were reduced by approximately 30% by Ex-9 after glucose ingestion (control, 1154 ± 203 vs. Ex-9, 835 ± 120 pmol/liter; P < 0.05). Blocking the action of endogenous GLP-1 caused an approximate 80% increase in postprandial glucagon concentrations. The appearance of ingested d-xylose in the blood was not affected by Ex-9, suggesting that postprandial secretion of GLP-1 has only minimal effects on gastric emptying of oral glucose. Conclusions: These findings indicate that GLP-1 is an incretin in healthy humans at modestly supraphysiological blood glucose levels. The primary effect of GLP-1 to regulate oral glucose tolerance is mediated by effects on islet hormones and not on gastric emptying.
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Method 3 allows for an estimate of the incretin effect in a single-day experiment.
“This method allows for an estimate of the incretin effect in a single-day experiment and has been employed in several previously published studies (9, 27).”
From Assessment of the incretin effect in healthy subjects: concordance between clamp and OGTT methods (2023) · cites this paper as [9]
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Cites
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425 · see citing works
Kieffer, T. J., & Habener, J. F. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.6.0385 · Cited by 1,056 · see citing works
NAUCK, M. A., HOMBERGER, E., SIEGEL, E. G., ALLEN, R. C., EATON, R. P., EBERT, R., & CREUTZFELDT, W. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-63-2-492 · Cited by 874 · see citing works
Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients
Toft-Nielsen, M.-B., Damholt, M. B., Madsbad, S., Hilsted, L. M., Hughes, T. E., Michelsen, B. K., & Holst, J. J. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.8.7750 · Cited by 869 · see citing works
Truncated GLP-1 (proglucagon 78?107-amide) inhibits gastric and pancreatic functions in man
Wettergren, A., Schjoldager, B., Mortensen, P. E., Myhre, J., Christiansen, J., & Holst, J. J. (1993) · Digestive Diseases and Sciences · doi:10.1007/bf01316798 · Cited by 670 · see citing works
Nauck, M. A., Heimesaat, M. M., Behle, K., Holst, J. J., Nauck, M. S., Ritzel, R., Hüfner, M., & Schmiegel, W. H. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.3.8355 · Cited by 605 · see citing works
Nauck, M. A., Bartels, E., Ørskov, C., Ebert, R., & Creutzfeldt, W. (1993) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.76.4.8473405 · Cited by 505 · see citing works
Vilsbøll, T., Krarup, T., Madsbad, S., & Holst, J. J. (2003) · Regulatory Peptides · doi:10.1016/s0167-0115(03)00111-3 · Cited by 430 · see citing works
Gastric emptying and release of incretin hormones after glucose ingestion in humans.
Schirra, J., Katschinski, M., Weidmann, C., Schäfer, T., Wank, U., Arnold, R., & Göke, B. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118411 · Cited by 426 · see citing works
Edwards, C. M., Todd, J. F., Mahmoudi, M., Wang, Z., Wang, R. M., Ghatei, M. A., & Bloom, S. R. (1999) · Diabetes · doi:10.2337/diabetes.48.1.86 · Cited by 344 · cited 6× · see citing works
“(7) demonstrated that blocking the GLP-1r increased the postprandial glucose AUC by 35% after a liquid glucose meal.”
BackgroundInfluentialCreutzfeldt, W., Kleine, N., Willms, B., Ørskov, C., Holst, J. J., & Nauck, M. A. (1996) · Diabetes Care · doi:10.2337/diacare.19.6.580 · Cited by 328 · see citing works
Näslund, E. B., Gutniak, M., Skogar, S., Rössner, S., & Hellström, P. M. (1998) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/68.3.525 · Cited by 307 · see citing works
Schirra, J., Nicolaus, M., Roggel, R., Katschinski, M., Storr, M., Woerle, H. J., & Göke, B. (2005) · Gut · doi:10.1136/gut.2004.059741 · Cited by 275 · see citing works
Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in humans
Schirra, J., Sturm, K., Leicht, P., Arnold, R., Göke, B., & Katschinski, M. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1349 · Cited by 265 · see citing works
Oral Glucose Augmentation of Insulin Secretion
Andersen, D. K., Elahi, D., Brown, J. C., Tobin, J. D., & Andres, R. (1978) · Journal of Clinical Investigation · doi:10.1172/jci109100 · Cited by 239 · see citing works
Delgado-Aros, S., Kim, D.-Y., Burton, D. D., Thomforde, G. M., Stephens, D., Brinkmann, B. H., Vella, A., & Camilleri, M. (2002) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2002.282.3.g424 · Cited by 235 · see citing works
GLP-1 Receptor Agonists and DPP-4 Inhibitors in the Treatment of Type 2 Diabetes
Åhrén, B., & Schmitz, O. (2004) · Hormone and Metabolic Research · doi:10.1055/s-2004-826178 · Cited by 227 · see citing works
Vella, A. V., Bock, G., Giesler, P. D., Burton, D. B., Serra, D. B., Ligueros‐Saylan, M., Dunning, B. E., Foley, J. E., Rizza, R. A., & Camilleri, M. (2007) · Diabetes · doi:10.2337/db07-0136 · Cited by 200 · see citing works
A simplified, colorimetric micromethod for xylose in serum or urine, with phloroglucinol.
Eberts, T. J., Sample, R. H. B., Glick, M. R., & Ellis, G. H. (1979) · Clinical Chemistry · doi:10.1093/clinchem/25.8.1440 · Cited by 199 · see citing works
Prigeon, R. L., Quddusi, S., Paty, B., & D'Alessio, D. A. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00024.2003 · Cited by 199 · see citing works
Self-citationD’Alessio, D. A., Vogel, R., Prigeon, R. L., Laschansky, E. C., Koerker, D. J., Eng, J., & Ensinck, J. W. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118380 · Cited by 118 · see citing works
Self-citationIs glucagon-like peptide 1 an incretin hormone?
Nauck, M. A. (1999) · Diabetologia · doi:10.1007/s001250051165 · Cited by 102 · see citing works
Tissot, S., Normand, S., Guilluy, R., Pachiaudi, C., Beylot, M., Laville, M., Cohen, R., Mornex, R., & Riou, J. P. (1990) · Diabetologia · doi:10.1007/bf00405104 · Cited by 90 · see citing works
Meier, J. J., Deacon, C. F., Schmidt, W. E., Holst, J. J., & Nauck, M. A. (2007) · Diabetologia · doi:10.1007/s00125-007-0598-z · Cited by 89 · see citing works
Elder, D. A., Prigeon, R. L., Wadwa, R. P., Dolan, L. M., & D’Alessio, D. A. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0853 · Cited by 78 · see citing works
Self-citationBardet, S., Pasqual, C., Maugendre, D., Remy, J. P., Charbonnel, B. H., & Saï, P. (1989) · PubMed · Cited by 27 · see citing works
Stimulation of the Small Intestine by Nutrients in Relation to Phase of the Migrating Motor Complex
Medhus, O. S. A. W. (2000) · Scandinavian Journal of Gastroenterology · doi:10.1080/003655200750023750 · Cited by 16 · see citing works
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Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease
Sandoval, D. A., & D'Alessio, D. A. (2015) · Physiological Reviews · doi:10.1152/physrev.00013.2014 · Cited by 498 · see citing works
Self-citationGLP-1 Receptor Activation Modulates Appetite- and Reward-Related Brain Areas in Humans
van Bloemendaal, L., IJzerman, R. G., ten Kulve, J. S., Barkhof, F., Konrad, R. J., Drent, M. L., Veltman, D. J., & Diamant, M. (2014) · Diabetes · doi:10.2337/db14-0849 · Cited by 427 · see citing works
GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes
Muskiet, M. H. A., Tonneijck, L., Smits, M. M., van Baar, M. J. B., Kramer, M. H. H., Hoorn, E. J., Joles, J. A., & van Raalte, D. H. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.123 · Cited by 407 · see citing works
Relationships Between Gastric Emptying, Postprandial Glycemia, and Incretin Hormones
Marathe, C. S., Rayner, C. K., Jones, K. L., & Horowitz, M. (2013) · Diabetes Care · doi:10.2337/dc12-1609 · Cited by 335 · see citing works
Salehi, M., Prigeon, R. L., & D’Alessio, D. A. (2011) · Diabetes · doi:10.2337/db11-0203 · Cited by 323 · see citing works
Self-citationGIP 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
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
Koska, J., Sands, M., Burciu, C., D’Souza, K. M., Raravikar, K., Liu, J., Truran, S., Franco, D. A., Schwartz, E. A., Schwenke, D. C., et al. (2015) · Diabetes · doi:10.2337/db14-0976 · Cited by 174 · see citing works
Self-citationEffects of GLP-1 and Incretin-Based Therapies on Gastrointestinal Motor Function
Marathe, C. S., Rayner, C. K., Jones, K. L., & Horowitz, M. (2011) · Experimental Diabetes Research · doi:10.1155/2011/279530 · Cited by 138 · see citing works
Effect of endogenous GLP-1 on insulin secretion in type 2 diabetes
Salehi, M., Aulinger, B., Prigeon, R. L., & D'Alessio, D. A. (2010) · Diabetes · doi:10.2337/db09-1253 · Cited by 124 · see citing works
Self-citationGlucagon-like peptides 1 and 2 in health and disease: A review
Marathe, C. S., Rayner, C. K., Jones, K. L., & Horowitz, M. (2013) · Peptides · doi:10.1016/j.peptides.2013.01.014 · Cited by 100 · see citing works
Smits, M. M., Tonneijck, L., Muskiet, M. H. A., Kramer, M. H. H., Cahen, D. L., & van Raalte, D. H. (2016) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12593 · Cited by 74 · see citing works
GLP‐1R and amylin agonism in metabolic disease: complementary mechanisms and future opportunities
Roth, J. D., Erickson, M. R., Chen, S., & Parkes, D. G. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01537.x · Cited by 74 · see citing works
GIP and GLP-1 receptor antagonism during a meal in healthy individuals
Gasbjerg, L. S., Helsted, M. M., Hartmann, B., Sparre-Ulrich, A. H., Veedfald, S., Stensen, S., Lanng, A. R., Bergmann, N. C., Christensen, M. B., Vilsbøll, T., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz175 · Cited by 68 · see citing works
Effect of Glucagon-like Peptide-1 Receptor Antagonism on Appetite and Food Intake in Healthy Men
Steinert, R. E., Schirra, J., Meyer-Gerspach, A. C., Kienle, P., Fischer, H., Schulte, F., Goeke, B., & Beglinger, C. (2014) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.114.083246 · Cited by 52 · see citing works
Intra-islet glucagon-like peptide 1
Fava, G. E., Dong, E. W., & Wu, H. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.05.016 · Cited by 45 · see citing works
Effect of Glycemia on Plasma Incretins and the Incretin Effect During Oral Glucose Tolerance Test
Salehi, M., Aulinger, B., & D’Alessio, D. A. (2012) · Diabetes · doi:10.2337/db11-1825 · Cited by 38 · see citing works
Self-citationChen, P., Yang, F., Wang, W., Li, X., Liu, D., Zhang, Y., Yin, G., Lv, F., Guo, Z., Mehta, J. L., et al. (2021) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248420942007 · Cited by 31 · see citing works
Lupoli, R., Creanza, A., Griffo, E., Nardone, G., Rocco, A., Bozzetto, L., Annuzzi, G., Riccardi, G., & Capaldo, B. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-02811 · Cited by 8 · see citing works
Assessment of the incretin effect in healthy subjects: concordance between clamp and OGTT methods
Aulinger, B. A., & D’Alessio, D. A. (2023) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00104.2022 · Cited by 6 · see citing works
Self-citation
- Authors
- Salehi, M., Vahl, T. P., & D'Alessio, D. A.
- Affiliations
- University of Cincinnati (US)
- University of Cincinnati, Department of Internal Medicine, Cincinnati, Ohio 45267
- Corresponding author
- Salehi, Marzieh
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-12-01
- Volume
- 93
- Issue
- 12
- Pages
- 4909-4916
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2626449
- OpenAlex
- W2069292466
- Cited by
- 108
- References
- 27
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 7 · 2021: 3 · 2020: 4 · 2019: 7 · 2018: 6 · 2017: 7 · 2016: 9 · 2015: 12 · 2014: 11 · 2013: 13 · 2012: 5
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cincinnati Children's Hospital Medical Center
- University of Cincinnati
- National Institutes of Health
- College of Medicine, University of Cincinnati
- National Institute of Diabetes and Digestive and Kidney Diseases (DK57900-05, R01DK057900)
- National Center for Research Resources (M01RR008084, M01-RR-08084)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- glucagon-like peptide-1, exendin-9-39, islet hormone secretion, insulin secretion, glucagon secretion, gastric emptying, glucose tolerance, incretins, hyperglycemia
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Adult, Algorithms, Blood Glucose, Female, Gastric Emptying, Glucose, Humans, Hyperglycemia, Infusions, Intravenous, Insulin, Islets of Langerhans, Male, Middle Aged, Pancreatic Hormones, Peptide Fragments, Xylose, Glucose Clamp Technique, Receptors, Glucagon, Area Under Curve, Glucagon-Like Peptide 1
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