Glucose-dependent insulinotropic polypeptide directly induces glucose transport in rat skeletal muscle

Snook, Laelie A.; Nelson, Emery M.; Dyck, David J.; Wright, David C.; Holloway, Graham P.

doi:10.1152/ajpregu.00003.2015

Cited by 17Metabolism, Diabetes, and CancerDiabetes Treatment and ManagementPancreatic function and diabetes

Glucose-dependent insulinotropic polypeptide directly induces glucose transport in rat skeletal muscle

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Snook, Laelie A., Nelson, Emery M., Dyck, David J., Wright, David C., Holloway, Graham P.·2015·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

DOI 10.1152/ajpregu.00003.2015PMC PMC4525324

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Abstract

Several gastrointestinal proteins have been identified to have insulinotropic effects, including glucose-dependent insulinotropic polypeptide (GIP); however, the direct effects of incretins on skeletal muscle glucose transport remain largely unknown. Therefore, the purpose of the current study was to examine the role of GIP on skeletal muscle glucose transport and insulin signaling in rats. Relative to a glucose challenge, a mixed glucose+lipid oral challenge increased circulating GIP concentrations, skeletal muscle Akt phosphorylation, and improved glucose clearance by ∼35% (P < 0.05). These responses occurred without alterations in serum insulin concentrations. In an incubated soleus muscle preparation, GIP directly stimulated glucose transport and increased GLUT4 accumulation on the plasma membrane in the absence of insulin. Moreover, the ability of GIP to stimulate glucose transport was mitigated by the addition of the PI 3-kinase (PI3K) inhibitor wortmannin, suggesting that signaling through PI3K is required for these responses. We also provide evidence that the combined stimulatory effects of GIP and insulin on soleus muscle glucose transport are additive. However, the specific GIP receptor antagonist (Pro(3))GIP did not attenuate GIP-stimulated glucose transport, suggesting that GIP is not signaling through its classical receptor. Together, the current data provide evidence that GIP regulates skeletal muscle glucose transport; however, the exact signaling mechanism(s) remain unknown.

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GIP promotes skeletal muscle absorption of glucose in murine experimental models, both in the resting state and following insulin stimulation, in a PI3K-dependent manner.
“Also, GIP seems to promote skeletal muscle’s absorption of glucose in murine experimental models, both in the resting state and following insulin stimulation, in a PI3K-dependent manner [57].”
From Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance (2024) · cites this paper as [57]

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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 · see citing works
Glucagon-like peptide-1 7–36: a physiological incretin in man
Kreymann, B., Ghatei, M. A., Williams, G., & Bloom, S. R. (1987) · The Lancet · doi:10.1016/s0140-6736(87)91194-9 · Cited by 1,928 · see citing works
Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus
Nauck, M. A., Heimesaat, M. M., Orskov, C., Holst, J. J., Ebert, R., & Creutzfeldt, W. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116186 · Cited by 1,651 · see citing works
Inhibition of gastric inhibitory polypeptide signaling prevents obesity
Miyawaki, K., Yamada, Y., Ban, N., Ihara, Y., Tsukiyama, K., Zhou, H., Fujimoto, S., Oku, A., Tsuda, K., Toyokuni, S., et al. (2002) · Nature Medicine · doi:10.1038/nm727 · Cited by 963 · see citing works
Insulinotropin: glucagon-like peptide I (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas.
Mojsov, S., Weir, G. C., & Habener, J. F. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112855 · Cited by 882 · see citing works
Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain.
Usdin, T. B., Mezey, E., Button, D. C., Brownstein, M. J., & Bonner, T. I. (1993) · Endocrinology · doi:10.1210/endo.133.6.8243312 · Cited by 534 · see citing works
Glucose intolerance caused by a defect in the entero-insular axis: A study in gastric inhibitory polypeptide receptor knockout mice
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 · see citing works
Molecular Mechanisms of Insulin Resistance: Serine Phosphorylation of Insulin Receptor Substrate-1 and Increased Expression of p85α
Draznin, B. (2006) · Diabetes · doi:10.2337/db06-0391 · Cited by 390 · see citing works
GLP-1 Receptor Activation Indirectly Reduces Hepatic Lipid Accumulation But Does Not Attenuate Development of Atherosclerosis in Diabetic Male ApoE−/− Mice
Panjwani, N., Mulvihill, E. E., Longuet, C., Yusta, B., Campbell, J. E., Brown, T. J., Streutker, C., Holland, D., Cao, X., Baggio, L. L., et al. (2013) · Endocrinology · doi:10.1210/en.2012-1937 · Cited by 346 · see citing works
Physiology and Pharmacology of the Enteroendocrine Hormone Glucagon-Like Peptide-2
Drucker, D. J., & Yusta, B. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170317 · Cited by 344 · see citing works
Identification and Actions of Gastric Inhibitory Polypeptide
Brown, J. C., Dryburgh, J. R., ROSS, S. A., & DUPRÉ, J. (1975) · Elsevier eBooks · doi:10.1016/b978-0-12-571131-9.50017-7 · Cited by 333 · see citing works
AS160 Regulates Insulin- and Contraction-stimulated Glucose Uptake in Mouse Skeletal Muscle
Kramer, H. F., Witczak, C. A., Taylor, E. B., FUJII, N. L., Hirshman, M. F., & Goodyear, L. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605461200 · Cited by 285 · see citing works
On the treatment of <i>Diabetus mellitus</i> by acid extract of Duodenal Mucous Membrane
Moore, B., Edie, E. S., & Abram, J. H. (1906) · Biochemical Journal · doi:10.1042/bj0010028 · Cited by 279 · see citing works
Abundance, localization, and insulin-induced translocation of glucose transporters in red and white muscle
Marette, A., Richardson, J. M., Ramlal, T., Balon, T. W., Vranić, M., Pessin, J. E., & Klip, A. (1992) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1992.263.2.c443 · Cited by 244 · see citing works
Wortmannin inhibits insulin‐stimulated but not contraction‐stimulated glucose transport activity in skeletal muscle
Lee, A. D., Hansen, P. A., & Holloszy, J. O. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00147-2 · Cited by 234 · see citing works
Insulin Signaling Diverges into Akt-dependent and -independent Signals to Regulate the Recruitment/Docking and the Fusion of GLUT4 Vesicles to the Plasma Membrane
Gonzalez, E., & McGraw, T. E. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-07-0585 · Cited by 210 · see citing works
G Protein–Coupled Receptor Deorphanizations
Civelli, O., Reinscheid, R. K., Zhang, Y., Wang, Z., Fredriksson, R., & Schiöth, H. B. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134548 · Cited by 191 · see citing works
Role of Akt substrate of 160 kDa in insulin-stimulated and contraction-stimulated glucose transport
Cartee, G. D., & Wojtaszewski, J. F. P. (2007) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h07-026 · Cited by 183 · see citing works
GIP-Overexpressing Mice Demonstrate Reduced Diet-Induced Obesity and Steatosis, and Improved Glucose Homeostasis
Kim, S.-J., Nian, C., Karunakaran, S., Clee, S. M., Isales, C. M., & McIntosh, C. H. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040156 · Cited by 182 · see citing works
GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice
Hansotia, T., & Drucker, D. J. (2004) · Regulatory Peptides · doi:10.1016/j.regpep.2004.07.019 · Cited by 182 · see citing works
Omega-3 supplementation alters mitochondrial membrane composition and respiration kinetics in human skeletal muscle
Herbst, E. A. F., Paglialunga, S., Gerling, C., Whitfield, J., Mukai, K., Chabowski, A., Heigenhauser, G. J. F., Spriet, L. L., & Holloway, G. P. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2013.267336 · Cited by 179 · see citing works
Self-citation
Glucose-Dependent Insulinotropic Polypeptide Enhances Adipocyte Development and Glucose Uptake in Part Through Akt Activation
Song, D. H., Getty–Kaushik, L., Tseng, E., Simon, J., Corkey, B. E., & Wolfe, M. M. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.09.005 · Cited by 137 · see citing works
Effects of the novel (Pro3)GIP antagonist and exendin(9–39)amide on GIP- and GLP-1-induced cyclic AMP generation, insulin secretion and postprandial insulin release in obese diabetic (ob/ob) mice: evidence that GIP is the major physiological incretin
Gault, V. A., O'Harte, F. P. M., Harriott, P., Mooney, M., Green, B., & Flatt, P. R. (2003) · Diabetologia · doi:10.1007/s00125-002-1028-x · Cited by 134 · see citing works
Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia
Smith, A. C., Mullen, K. L., Junkin, K. A., Nickerson, J., Chabowski, A., Bonen, A., & Dyck, D. J. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00677.2006 · Cited by 127 · see citing works
Self-citation
The Glucagon-Like Peptide-1 Receptor Regulates Endogenous Glucose Production and Muscle Glucose Uptake Independent of Its Incretin Action
Ayala, J. E., Bracy, D. P., James, F. D., Julien, B. M., Wasserman, D. H., & Drucker, D. J. (2008) · Endocrinology · doi:10.1210/en.2008-0945 · Cited by 114 · see citing works
On the causation of the so-called ‘peripheral reflex secretion’ of the pancreas. (Preliminary communication.)
Bayliss, W. M., & Starling, E. H. (1902) · Proceedings of the Royal Society of London · doi:10.1098/rspl.1901.0119 · Cited by 100 · see citing works
Muscle lactate transport studied in sarcolemmal giant vesicles
Juel, C. (1991) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(91)90004-r · Cited by 100 · see citing works
Experimental approaches in muscle metabolism: hindlimb perfusion and isolated muscle incubations
Bonen, A., Clark, M. G., & Henriksen, E. J. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.1.e1 · Cited by 91 · see citing works
GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle
Sjøberg, K. A., Holst, J. J., Rattigan, S., Richter, E. A., & Kiens, B. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00283.2013 · Cited by 69 · see citing works
Intracellular Delivery of Phosphatidylinositol (3,4,5)-Trisphosphate Causes Incorporation of Glucose Transporter 4 into the Plasma Membrane of Muscle and Fat Cells without Increasing Glucose Uptake
Sweeney, G., Garg, R. R., Ceddia, R. B., Li, D., Ishiki, M., Somwar, R., Foster, L. J., Neilsen, P. O., Prestwich, G. D., Rudich, A., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402897200 · Cited by 66 · see citing works
The transferrin receptor defines two distinct contraction-responsive GLUT4 vesicle populations in skeletal muscle.
Lemieux, K., Han, X. X., Dombrowski, L., Bonen, A., & Marette, A. (2000) · Diabetes · doi:10.2337/diabetes.49.2.183 · Cited by 63 · see citing works
Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion
Shibue, K., Yamane, S., Harada, N., Hamasaki, A., Suzuki, K., Joo, E., Iwasaki, K., Nasteska, D., Harada, T., Hayashi, Y., et al. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00543.2014 · Cited by 61 · see citing works
Gastric inhibitory polypeptide and effects of glycation on glucose transport and metabolism in isolated mouse abdominal muscle
O'Harte, F., Gray, A., & Flatt, P. (1998) · Journal of Endocrinology · doi:10.1677/joe.0.1560237 · Cited by 60 · see citing works
Subcellular Localization of GLUT4 in Nonstimulated and Insulin-Stimulated Soleus Muscle of Rat
Bornemann, A., Ploug, T., & Schmalbruch, H. (1992) · Diabetes · doi:10.2337/diab.41.2.215 · Cited by 58 · see citing works
A Transgenic Mouse Model to Study Glucose Transporter 4myc Regulation in Skeletal Muscle
Schertzer, J. D., Antonescu, C. N., Bilan, P. J., Jain, S., Huang, X., Liu, Z., Bonen, A., & Klip, A. (2008) · Endocrinology · doi:10.1210/en.2008-1372 · Cited by 48 · see citing works
Comparison of peripheral glucose uptake after oral glucose loading and a mixed meal
Jackson, R. A., BLIX, P. M., Matthews, J. A., Morgan, L., Rubenstein, A. H., & Nabarro, J. D. N. (1983) · Metabolism · doi:10.1016/0026-0495(83)90128-2 · Cited by 47 · see citing works
Genetic inactivation of GIP signaling reverses aging-associated insulin resistance through body composition changes
Yamada, C., Yamada, Y., Tsukiyama, K., Yamada, K., Yamane, S., Harada, N., Miyawaki, K., Seino, Y., & Inagaki, N. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.09.128 · Cited by 43 · see citing works
Extrapancreatic action of truncated glucagon-like peptide-I in otsuka long-evans tokushima fatty rats, an animal model for non—insulin-dependent diabetes mellitus
Mizuno, A., Kuwajima, M., Ishida, K., et al. (1997) · Metabolism · doi:10.1016/s0026-0495(97)90117-7 · Cited by 32 · see citing works
Gi-mediated translocation of GLUT4 is independent of p85/p110α and p110γ phosphoinositide 3-kinases but might involve the activation of Akt kinase
Wang, L., Hayashi, H., Kishi, K., et al. (2000) · Biochemical Journal · doi:10.1042/bj3450543 · Cited by 28 · see citing works
Differential effects of glucagon‐like peptide‐1 on microvascular recruitment and glucose metabolism in short‐ and long‐term insulin resistance
Sjøberg, K. A., Rattigan, S., Jeppesen, J. F., Lundsgaard, A., Holst, J. J., & Kiens, B. (2015) · The Journal of Physiology · doi:10.1113/jp270129 · Cited by 27 · see citing works
Effects of glucagon-like peptide-1 (7-36)amide on insulin stimulated rat skeletal muscle glucose transport
Hansen, B. F., Jensen, P. B., Nepper-Christensen, E., & Skjølstrup, B. (1998) · Acta Diabetologica · doi:10.1007/s005920050112 · Cited by 19 · see citing works
The role of incretin-based therapies in prediabetes: A review
Ahmadieh, H., & Azar, S. T. (2014) · Primary care diabetes · doi:10.1016/j.pcd.2014.02.005 · Cited by 18 · see citing works
Participation of Protein Kinases in the Stimulant Action of GLP-1 on 2-deoxy-D-glucose Uptake by Normal Rat Skeletal Muscle
Acitores, A., González, N., Sancho, V., et al. (2005) · Hormone and Metabolic Research · doi:10.1055/s-2005-861469 · Cited by 14 · see citing works
Effect of glucose‐dependent insulinotropic polypeptide on whole‐body glucose utilization in sheep
Rose, M. T., Itoh, F., & Takahashi, Y. K. (1998) · Experimental Physiology · doi:10.1113/expphysiol.1998.sp004159 · Cited by 7 · see citing works

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Authors: Snook, L. A., Nelson, E. M., Dyck, D. J., Wright, D. C., & Holloway, G. P.
Affiliations: University of Guelph (CA)
Corresponding author: Holloway, Graham P.
ORCID: Snook, Laelie A.
Dyck, David J.
Wright, David C.
Holloway, Graham P.
Venue: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Publisher: American Physiological Society
Published: 2015-08-01
Volume: 309
Issue: 3
Pages: R295-R303
ISSN: 0363-6119 (ISSN-L)
1522-1490
DOI: 10.1152/ajpregu.00003.2015
PMC: PMC4525324
OpenAlex: W2226908594
Cited by: 17
References: 44
Citations by year: 2026: 2 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 2 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1
FWCI: 0.29
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: NSERC (03656, 341158)
CFI (25136, 218463)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords: glucose-dependent insulinotropic polypeptide, skeletal muscle glucose transport, GLUT4 translocation, PI3K signaling, Akt phosphorylation, incretins, insulin signaling, glucose clearance, soleus muscle, GIP receptor, wortmannin
MeSH terms: Animals, Biological Transport, Gastric Inhibitory Polypeptide, Glucose, Insulin, Male, Receptors, Gastrointestinal Hormone, Rats, Sprague-Dawley, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Glucose Transporter Type 4

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Glucose-dependent insulinotropic polypeptide directly induces glucose transport in rat skeletal muscle

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