Glucose-Dependent Insulinotropic Polypeptide Stimulation of Lipolysis in Differentiated 3T3-L1 Cells: Wortmannin-Sensitive Inhibition by Insulin**This work was supported by grants from Zymogenetics Inc. (Seattle, WA), the Medical Research Council of Canada (5–90007-RAP/CHSM) and the Canadian Diabetes Association (CHSM/RAP).

McIntosh, Christopher H. S.; Bremsak, Irene; Lynn, Francis C.; Gill, Ruth; Hinke, Simon A.; Gelling, Richard; Nian, Cuilan; McKnight, Gary; Jaspers, Stephen; Pederson, Raymond A.

doi:10.1210/endo.140.1.6464

Cited by 73Lipid metabolism and biosynthesisAdipose Tissue and MetabolismMetabolism, Diabetes, and Cancer

Glucose-Dependent Insulinotropic Polypeptide Stimulation of Lipolysis in Differentiated 3T3-L1 Cells: Wortmannin-Sensitive Inhibition by Insulin**This work was supported by grants from Zymogenetics Inc. (Seattle, WA), the Medical Research Council of Canada (5–90007-RAP/CHSM) and the Canadian Diabetes Association (CHSM/RAP).

McIntosh, Christopher H. S., Bremsak, Irene, Lynn, Francis C., Gill, Ruth, Hinke, Simon A., Gelling, Richard, Nian, Cuilan, McKnight, Gary +2 more·1999·Endocrinology

DOI 10.1210/endo.140.1.6464

Open this paper in CoChat — free account

Abstract

GIP is an important insulinotropic hormone (incretin) that has also been implicated in fat metabolism. There is controversy regarding the actions of GIP on adipocytes. In the current study, the existence of GIP receptors and effects of GIP on lipolysis were studied in differentiated 3T3-L1 cells. GIP receptor messenger RNA was detected by RT-PCR and RNase protection assay. Receptors were detected in binding studies (IC50 26.7 +/- 0.7 nM). GIP stimulated glycerol release with an EC50 of 3.28 +/- 0.63 nM. GIP (10(-9)-10(-7) M) +/- IBMX increased cAMP production by 1180-2246%. The adenylyl cyclase inhibitor MDL 12330A (10(-4) M) inhibited GIP-induced glycerol production by >90%, and reduced cAMP responses to basal. Preincubation of 3T3-L1 cells with insulin inhibited glycerol responses to GIP, and the inhibitory effect of insulin was blocked by the phosphatidylinositol 3'-kinase inhibitor, wortmannin. It is concluded that GIP stimulates glycerol release in 3T3-L1 cells primarily via stimulation of cAMP production, and that insulin antagonizes GIP-induced lipolysis in a wortmannin-sensitive fashion. It is suggested that effects of GIP on fat metabolism in vivo may depend upon the circulating insulin level, and that meal-released GIP may elevate circulating fatty acids, thus optimizing pancreatic beta-cell responsiveness to stimulation by glucose and GIP.

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

Crossref · 10.1210/endo.140.1.6464

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

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?

GIP promotes lipogenesis and lipid deposition under hyperinsulinemia while stimulating lipolysis and fatty acid oxidation under normo- or hypoinsulinemia.
“GIP promotes lipogenesis and lipid deposition under conditions of hyperinsulinema [34–36] while stimulating lipolysis and fatty acid oxidation under conditions of normo- or hypoinsulinemia [37–39].”
From Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes (2024) · cites this paper as [38]
The Discussion (page unavailable) reports that GIP stimulated lipolysis in 3T3-L1 cells without insulin and that insulin inhibited this effect. It proposes that GIP may stimulate lipolysis when insulin levels are too low to inhibit it, but does not establish fatty acid oxidation. The hyperinsulinemia clause is attached to different citations and is not assessed here. (LLM, conf=0.87)
Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,240 · see citing works
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczyński, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 47,092 · see citing works
Signalling through the lipid products of phosphoinositide-3-OH kinase
Toker, A., & Cantley, L. C. (1997) · Nature · doi:10.1038/42648 · Cited by 1,314 · see citing works
Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin.
Okada, T., Kawano, Y., Sakakibara, T., Hazeki, O., & Ui, M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41901-6 · Cited by 917 · see citing works
The insulin signalling system and the IRS proteins
White, M. F. (1997) · Diabetologia · doi:10.1007/s001250051387 · Cited by 581 · see citing works
Peptides and Protein Phosphorylation
Kemp, B. E. (2018) · CRC Press eBooks · doi:10.1201/9781351075442 · Cited by 522 · see citing works
Structure, Localization, and Regulation of cGMP-inhibited Phosphodiesterase (PDE3)
Degerman, E., Belfrage, P., & Manganiello, V. C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.11.6823 · Cited by 432 · see citing works
Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat.
Stein, D. T., Esser, V., Stevenson, B. E., Lane, K. E., Whiteside, J. H., Daniels, M. B., Chen, S., & McGarry, J. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118727 · Cited by 367 · see citing works
Regulation of ob gene mRNA levels in cultured adipocytes
Rentsch, J., & Chiesi, M. (1996) · FEBS Letters · doi:10.1016/0014-5793(95)01485-3 · Cited by 259 · see citing works
The phosphatidylinositol 3-kinase serine kinase phosphorylates IRS-1. Stimulation by insulin and inhibition by Wortmannin.
Lam, K., Carpenter, C. L., Ruderman, N. B., Friel, J., & Kelly, K. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32042-2 · Cited by 232 · see citing works
Gastric Inhibitory Polypeptide Enhanced Lipoprotein Lipase Activity in Cultured Preadipocytes
Eckel, R. H., Fujimoto, W. Y., & Brunzell, J. D. (1979) · Diabetes · doi:10.2337/diab.28.12.1141 · Cited by 219 · see citing works
Hormone-sensitive lipase — A multipurpose enzyme in lipid metabolism
Yeaman, S. J. (1990) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(90)90067-n · Cited by 217 · see citing works
Handbook of Physiology, Section 6: The Gastrointestinal System
Greenberger, N. J. (1993) · JAMA · doi:10.1001/jama.1993.03500160119051 · Cited by 211 · see citing works
Gastric Inhibitory Polypeptide
Brown, J. C. (1982) · Monographs on endocrinology · doi:10.1007/978-3-642-81771-7 · Cited by 171 · see citing works
Effect of gastric inhibitory polypeptide on plasma levels of chylomicron triglycerides in dogs.
Wasada, T., McCorkle, K., Harris, V., Kawai, K., Howard, B. V., & Unger, R. H. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110335 · Cited by 153 · see citing works
Insulin‐induced dephosphorylation of hormone‐sensitive lipase
Strålfors, P., & Honnor, R. C. (1989) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1989.tb14842.x · Cited by 151 · see citing works
Glucose-fatty acid interactions in health and disease
Jd, M. (1998) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/67.3.500s · Cited by 146 · see citing works
Subcutaneous Injection of the Incretin Hormone Glucagon-Like Peptide 1 Abolishes Postprandial Glycemia in NIDDM
Gutniak, M., Linde, B., Holst, J. J., & Efendić, S. (1994) · Diabetes Care · doi:10.2337/diacare.17.9.1039 · Cited by 139 · see citing works
Functional expression of the rat pancreatic islet glucose-dependent insulinotropic polypeptide receptor: ligand binding and intracellular signaling properties.
Wheeler, M. B., Gelling, R. W., McIntosh, C. H., Georgiou, J., Brown, J. C., & Pederson, R. A. (1995) · Endocrinology · doi:10.1210/endo.136.10.7664683 · Cited by 130 · see citing works
Self-citation
Reversal of impaired GIP and insulin secretion in patients with pancreatogenic steatorrhea following enzyme substitution
Ebert, R., & Creutzfeldt, W. (1980) · Diabetologia · doi:10.1007/bf00275269 · Cited by 125 · see citing works
The β-Adrenergic Receptor Is a Substrate for the Insulin Receptor Tyrosine Kinase
Baltensperger, K., Karoor, V., Paul, H., Ruoho, A. E., Czech, M., & Malbon, C. C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.2.1061 · Cited by 99 · see citing works
Effects of gastric inhibitory polypeptide on glucose and lipid metabolism of isolated rat adipocytes
Hauner, H., Glatting, G., Kaminska, D., & Pfeiffer, E. F. (1988) · Annals of Nutrition and Metabolism · doi:10.1159/000177467 · Cited by 98 · see citing works
Gastric inhibitory polypeptide (GIP)
O’Dorisio, T. M., Cataland, S., Stevenson, M., & Mazzaferri, E. L. (1976) · Digestive Diseases and Sciences · doi:10.1007/bf01073027 · Cited by 88 · see citing works
Hormone-sensitive lipase in differentiated 3T3-L1 cells and its activation by cyclic AMP-dependent protein kinase.
Kawamura, M., Jensen, D., Wancewicz, E. V., Joy, L. L., Khoo, J. C., & Steinberg, D. H. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.2.732 · Cited by 85 · see citing works
Differentiation-dependent expression of catecholamine-stimulated adenylate cyclase. Roles of the beta-receptor and G/F protein in differentiating 3T3-L1 adipocytes.
Lai, E. K., Rosen, O. M., & Rubin, C. S. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42976-6 · Cited by 82 · see citing works
Effect of Exogenous or Endogenous Gastric Inhibitory Polypeptide (GIP) on Plasma Triglyceride Responses in Rats
Ebert, R., Nauck, M. A., & Creutzfeldt, W. (1991) · Hormone and Metabolic Research · doi:10.1055/s-2007-1003745 · Cited by 79 · see citing works
The Incretin Notion and its Relevance to Diabetes
Habener, J. F. (1993) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(18)30135-x · Cited by 76 · see citing works
Phosphorylation of Tyrosyl Residues 350/354 of the β-Adrenergic Receptor Is Obligatory for Counterregulatory Effects of Insulin
Karoor, V., Baltensperger, K., Paul, H., Czech, M., & Malbon, C. C. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.43.25305 · Cited by 72 · see citing works
Hormone-sensitive particulate cAMP phosphodiesterase activity in 3T3-L1 adipocytes. Regulation of responsiveness by dexamethasone.
Elks, M. L., Manganiello, V. C., & Vaughan, M. J. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32095-7 · Cited by 71 · see citing works
Recent Studies of the 3T3-L1 Adipocyte-Like Cell Line
Rosen, O. M., Smith, C. J., Hirsch, A. H., Lai, E. K., & Rubin, C. S. (1979) · Elsevier eBooks · doi:10.1016/b978-0-12-571135-7.50015-1 · Cited by 65 · see citing works
Gastric inhibitory polypeptide: a gut hormone with anabolic functions
Beck, B. (1989) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0020169 · Cited by 54 · see citing works
Regulation of glucose transporters and hexose uptake in 3T3-L1 adipocytes: glucagon-like peptide-1 and insulin interactions
Wang, Y., Hk, K., Montrose‐Rafizadeh, C., Perfetti, R., Bernier, M., & Egan, J. (1997) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0190241 · Cited by 54 · see citing works
Inhibition of actions of glucagon in adipocytes by gastric inhibitory polypeptide
Dupre, J., Greenidge, N., McDonald, T. J., Ross, S. A., & Rubinstein, D. (1976) · Metabolism · doi:10.1016/s0026-0495(76)80002-9 · Cited by 53 · see citing works
Localization of the Domains Involved in Ligand Binding and Activation of the Glucose-Dependent Insulinotropic Polypeptide Receptor
Gelling, R. W., Wheeler, M. B., Xue, J., Gyomorey, S., Nian, C., Pederson, R. A., & McIntosh, C. H. S. (1997) · Endocrinology · doi:10.1210/endo.138.6.9104 · Cited by 51 · see citing works
Self-citation
Gastric Inhibitory Polypeptide Activates MAP Kinase through the Wortmannin-Sensitive and -Insensitive Pathways
Kubota, A., Yamada, Y., Yasuda, K., Someya, Y., Ihara, Y., Kagimoto, S., Watanabe, R., Kuroe, A., Ishida, H., & Seino, Y. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6743 · Cited by 49 · see citing works
The importance of triglyceride hydrolysis for the release of gastric inhibitory polypeptide
Ross, S. A., & Shaffer, E. A. (1981) · Gastroenterology · doi:10.1016/0016-5085(81)90199-2 · Cited by 48 · see citing works
Lipolytic stimulation modulates the subcellular distribution of hormone-sensitive lipase in 3T3-L1 cells.
Hirsch, A. H., & Rosen, O. M. (1984) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37755-5 · Cited by 47 · see citing works
Gastric Inhibitory Polypeptide
Brown, J. C., Buchan, A. M. J., McIntosh, C. H. S., & Pederson, R. A. (1989) · Comprehensive physiology · doi:10.1002/cphy.cp060218 · Cited by 46 · see citing works
Self-citation
The effects of wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, on insulin-stimulated glucose transport, GLUT4 translocation, antilipolysis, and DNA synthesis
Evans, J. L., Honer, C. M., Womelsdorf, B. E., Kaplan, E. L., & Bell, P. A. (1995) · Cellular Signalling · doi:10.1016/0898-6568(95)00007-c · Cited by 40 · see citing works
Glucose-Dependent Insulinotropic Polypeptide Stimulates Insulin Secretion via Increased Cyclic AMP and [Ca2+]iand a Wortmannin-Sensitive Signalling Pathway
Straub, S. G., & Sharp, G. W. G. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1035 · Cited by 36 · see citing works
EFFECTS OF RMI 12330A, A NEW INHIBITOR OF ADENYLATE CYCLASE ON MYOCARDIAL FUNCTION AND SUBCELLULAR ACTIVITY
Grupp, G., Grupp, I. L., Johnson, C. L., Matlib, M. A., ROUSLIN, W., Schwartz, A., Wallick, E. T., Wang, T., & Wisler, P. L. (1980) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1980.tb08721.x · Cited by 31 · see citing works
GIP receptors and signal‐transduction mechanisms
McIntosh, C. H. S., Wheeler, M. B., Gelling, R. W., Brown, J. C., & Pederson, R. A. (1996) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1996.44267000.x · Cited by 26 · see citing works
Self-citation
Up-regulation of Ca2+ influx mediated by store-operated channels in HL60 cells induced to differentiate by 1α,25-Dihydroxyvitamin D3
Gardner, J. P., Balasubramanyam, M., & Studzinski, G. P. (1997) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(199709)172:3 · Cited by 24 · see citing works
Melatonin biosynthesis in photoreceptor-enriched chick retinal cell cultures: role of cyclic amp in the K+-evoked, ca2+ -dependent induction of serotonin n-acetyltransferase activity
Gan, J., Alonso-Gómez, A. L., Avendano, G., Johnson, B., & Iuvone, P. M. (1995) · Neurochemistry International · doi:10.1016/0197-0186(95)00035-7 · Cited by 21 · see citing works
Metabolic Effects of Gastric Inhibitory Polypeptide
Ebert, R., & Creutzfeldt, W. (2015) · Frontiers of hormone research · doi:10.1159/000414308 · Cited by 11 · see citing works
Secretion of Gastric Inhibitory Polypeptide in Patients with Bile Duct Obstruction
Yoshidome, K., Miyata, M., Izukura, M., Mizutani, S., Sakamoto, T., Tominaga, H., & Matsuda, H. (1995) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365529509089794 · Cited by 7 · see citing works
Control of Insulin Biosynthesis in the Human Fetal Beta Cell
Simpson, A. M., & Tuch, B. E. (1995) · Pancreas · doi:10.1097/00006676-199507000-00005 · Cited by 7 · see citing works

Flagged first, then by citations

2 of the 49 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

Wieland O 1974 Glycerol U.V. method. In: Burgmeyer HU (ed) Methods of Enzymatic Analysis. Academic Press, New York, vol 4:1404 -1409
Flakoll P, Carlson MG, Cherrington A 1996 Physiologic action of insulin. In: LeRoith D, Taylor SI, Olefsky JM (eds) Diabetes Mellitus. Lippincott-Raven, Philadelphia, pp 121-132

Sorted by citations

Molecular Mechanisms Regulating Hormone-Sensitive Lipase and Lipolysis
Holm, C., Østerlund, T., Laurell, H., & Contreras, J. A. (2000) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.20.1.365 · Cited by 565 · see citing works
International Union of Pharmacology. XXXV. The Glucagon Receptor Family
Mayo, K. E., Miller, L. J., BATAILLE, D., Dalle, S., Göke, B., Thorens, B., & Drucker, D. J. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.1.6 · Cited by 507 · see citing works
Dipeptidyl peptidase IV (DPP IV) inhibitors: a newly emerging drug class for the treatment of type 2 diabetes
Green, B. D., Flatt, P. R., & Bailey, C. J. (2006) · Diabetes and Vascular Disease Research · doi:10.3132/dvdr.2006.024 · Cited by 225 · see citing works
Activation of Lipoprotein Lipase by Glucose-dependent Insulinotropic Polypeptide in Adipocytes
Kim, S.-J., Nian, C., & McIntosh, C. H. S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609088200 · Cited by 216 · see citing works
Self-citation
Glucose-dependent insulinotropic polypeptide may enhance fatty acid re-esterification in subcutaneous abdominal adipose tissue in lean humans
Asmar, M., Simonsen, L., Madsbad, S., Stallknecht, B., Holst, J. J., & Bülow, J. (2010) · Diabetes · doi:10.2337/db10-0098 · Cited by 184 · 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
Self-citation
Chapter 15 Glucose‐Dependent Insulinotropic Polypeptide (Gastric Inhibitory Polypeptide; GIP)
McIntosh, C. H. S., Widenmaier, S. B., & Kim, S. (2009) · Vitamins and hormones · doi:10.1016/s0083-6729(08)00615-8 · Cited by 172 · see citing works
Self-citation
Glucose-Dependent Insulinotropic Polypeptide Promotes β-(INS-1) Cell Survival via Cyclic Adenosine Monophosphate-Mediated Caspase-3 Inhibition and Regulation of p38 Mitogen-Activated Protein Kinase
Ehses, J. A., Casilla, V. R., Doty, T., Pospisilik, J. A., Winter, K. D., Demuth, H., Pederson, R. A., & McIntosh, C. H. S. (2003) · Endocrinology · doi:10.1210/en.2002-0068 · Cited by 159 · see citing works
Self-citation
Targeting the glucagon receptor family for diabetes and obesity therapy
Cho, Y. M., Merchant, C. E., & Kieffer, T. J. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.05.009 · Cited by 142 · see citing works
Tirzepatide modulates the regulation of adipocyte nutrient metabolism through long-acting activation of the GIP receptor
Regmi, A., Aihara, E., Christe, M. E., Varga, G., Beyer, T. P., Ruan, X., Beebe, E., O’Farrell, L. S., Bellinger, M. A., Austin, A. K., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.05.010 · Cited by 135 · see citing works
Glucose-dependent insulinotropic polypeptide modulates adipocyte lipolysis and reesterification
Getty‐Kaushik, L., Song, D. H., Boylan, M. O., Corkey, B. E., & Wolfe, M. M. (2006) · Obesity · doi:10.1038/oby.2006.129 · Cited by 134 · see citing works
Targeting the GIPR for obesity: To agonize or antagonize? Potential mechanisms
Campbell, J. E. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101139 · Cited by 133 · see citing works
GIP increases human adipocyte LPL expression through CREB and TORC2-mediated trans-activation of the LPL gene
Kim, S.-J., Nian, C., & McIntosh, C. H. S. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m006841 · Cited by 133 · see citing works
Self-citation
Nutrient detection by incretin hormone secreting cells
Diakogiannaki, E., Gribble, F. M., & Reimann, F. M. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.12.001 · Cited by 123 · see citing works
Resistin Is a Key Mediator of Glucose-dependent Insulinotropic Polypeptide (GIP) Stimulation of Lipoprotein Lipase (LPL) Activity in Adipocytes
Kim, S.-J., Nian, C., & McIntosh, C. H. S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704896200 · Cited by 118 · see citing works
Self-citation
Human GIP(3-30)NH2 inhibits G protein-dependent as well as G protein-independent signaling and is selective for the GIP receptor with high-affinity binding to primate but not rodent GIP receptors
Gabe, M. B. N., Sparre‐Ulrich, A. H., Pedersen, M. F., Gasbjerg, L. S., Inoue, A., Bräuner‐Osborne, H., Hartmann, B., & ROSENKILDE, M. M. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.01.040 · Cited by 97 · see citing works
Glucose-dependent insulinotropic polypeptide receptor therapies for the treatment of obesity, do agonists=antagonists?
Killion, E. A., Lu, S.-C., Fort, M., Yamada, Y., Véniant, M. M., & Lloyd, D. J. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnz002 · Cited by 94 · see citing works
Glucose-dependent insulinotropic polypeptide (GIP)
Müller, T. D., Adriaenssens, A. E., Ahrén, B., Blüher, M., Birkenfeld, A. L., Campbell, J. E., Coghlan, M. P., D’Alessio, D. D., Deacon, C. F., DelPrato, S., et al. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102118 · Cited by 99 · see citing works
A novel pathway for regulation of glucose‐dependent insulinotropic polypeptide receptor expression in β‐cells
Lynn, F. C., Thompson, S. A., Pospisilik, J. A., Ehses, J. A., Hinke, S. A., Pamir, N., McIntosh, C. H. S., & Pederson, R. A. (2003) · The FASEB Journal · doi:10.1096/fj.02-0243fje · Cited by 91 · see citing works
Self-citation
Glucose-dependent insulinotropic polypeptide induces cytokine expression, lipolysis, and insulin resistance in human adipocytes
Timper, K., Grisouard, J., Sauter, N. S., Herzog-Radimerski, T., Dembinski, K., Peterli, R., Frey, D. M., Zulewski, H., Keller, U., Müller, B., et al. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00100.2012 · Cited by 88 · see citing works
Somatostatin receptor 5 and cannabinoid receptor 1 activation inhibit secretion of glucose-dependent insulinotropic polypeptide from intestinal K cells in rodents
Hodge, D., Marsh, W. J., Parker, H. E., Ogunnowo-Bada, E., Riches, C. H., Habib, A. M., Evans, M. L., Gribble, F. M., & Reimann, F. M. (2012) · Diabetologia · doi:10.1007/s00125-012-2663-5 · Cited by 87 · see citing works
Regulation of AMP-activated protein kinase activity by G-protein coupled receptors: Potential utility in treatment of diabetes and heart disease
Hutchinson, D. S., Summers, R. J., & Bengtsson, T. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.05.008 · Cited by 85 · see citing works
The influence of Glucose-dependent Insulinotropic Polypeptide (GIP) on human adipose tissue and fat metabolism: Implications for obesity, type 2 diabetes and Non-Alcoholic Fatty Liver Disease (NAFLD)
Thondam, S. K., Cuthbertson, D. J., & Wilding, J. P. H. (2020) · Peptides · doi:10.1016/j.peptides.2019.170208 · Cited by 77 · see citing works
Glucose-dependent insulinotropic polypeptide (GIP) and cardiovascular disease
Heimbürger, S. M., Bergmann, N. C., Augustin, R., Gasbjerg, L. S., Christensen, M. B., & Knop, F. K. (2020) · Peptides · doi:10.1016/j.peptides.2019.170174 · Cited by 67 · see citing works
Functional expression of glucose-dependent insulinotropic polypeptide receptors is coupled to differentiation in a human adipocyte model
Weaver, R. E., Donnelly, D., Wabitsch, M., Grant, P. J., & Balmforth, A. J. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.148 · Cited by 63 · see citing works
Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes
Gutgesell, R. M., Nogueiras, R., Tschöp, M. H., & Müller, T. D. (2024) · Diabetes Therapy · doi:10.1007/s13300-024-01566-x · Cited by 61 · see citing works
A New Pathway for Glucose-dependent Insulinotropic Polypeptide (GIP) Receptor Signaling
Ehses, J. A., Lee, S. S. T., Pederson, R. A., & McIntosh, C. H. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103023200 · Cited by 61 · see citing works
Self-citation
Adipocyte expression of the glucose-dependent insulinotropic polypeptide receptor involves gene regulation by PPARγ and histone acetylation
Kim, S., Nian, C., & McIntosh, C. H. S. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m012203 · Cited by 58 · see citing works
Self-citation
Glucose‐dependent insulinotropic polypeptide signaling in pancreatic β‐cells and adipocytes
McIntosh, C. H. S., Widenmaier, S. B., & Kim, S. (2012) · Journal of Diabetes Investigation · doi:10.1111/j.2040-1124.2012.00196.x · Cited by 58 · see citing works
Self-citation
Glucose‐dependent insulinotropic peptide impairs insulin signaling <i>via</i> inducing adipocyte inflammation in glucose‐dependent insulinotropic peptide receptor‐overexpressing adipocytes
Nie, Y., Ma, R. C., Chan, J. C. N., Xu, H., & Xu, G. (2012) · The FASEB Journal · doi:10.1096/fj.11-196782 · Cited by 53 · see citing works
Glucose-Dependent Insulinotropic Polypeptide Reduces Fat-Specific Expression and Activity of 11β-Hydroxysteroid Dehydrogenase Type 1 and Inhibits Release of Free Fatty Acids
Gögebakan, Ö., Andres, J., Biedasek, K., Mai, K., Kühnen, P., Krude, H., Isken, F., Rudovich, N. N., Osterhoff, M. A., Kintscher, U., et al. (2011) · Diabetes · doi:10.2337/db10-0902 · Cited by 51 · see citing works
A compendium of G-protein–coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure
Ceddia, R. P., & Collins, S. (2020) · Clinical Science · doi:10.1042/cs20190579 · Cited by 51 · see citing works
Inhibition of dipeptidyl peptidase IV activity as a therapy of Type 2 diabetes
Green, B. D., Flatt, P. R., & Bailey, C. J. (2006) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.11.3.525 · Cited by 50 · see citing works
Transgenic Rescue of Adipocyte Glucose-dependent Insulinotropic Polypeptide Receptor Expression Restores High Fat Diet-induced Body Weight Gain
Ugleholdt, R., Pedersen, J., Bassi, M. R., Füchtbauer, E., Jørgensen, S. M., Kissow, H., Nytofte, N., Poulsen, S. S., ROSENKILDE, M. M., Seino, Y., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.311779 · Cited by 49 · see citing works
Pleiotropic Actions of the Incretin Hormones
McIntosh, C. H. S., Widenmaier, S. B., & Kim, S. (2010) · Vitamins and hormones · doi:10.1016/b978-0-12-381517-0.00002-3 · Cited by 40 · see citing works
Self-citation
GIP’s involvement in the pathophysiology of type 2 diabetes
Christensen, M. B., Gasbjerg, L. S., Heimbürger, S. M., Stensen, S., Vilsbøll, T., & Knop, F. K. (2020) · Peptides · doi:10.1016/j.peptides.2019.170178 · Cited by 35 · see citing works
Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats
Baldassano, S., Gasbjerg, L. S., Kizilkaya, H. S., ROSENKILDE, M. M., Holst, J. J., & Hartmann, B. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00492 · Cited by 33 · see citing works
Dual Effects of Pituitary Adenylate Cyclase-Activating Polypeptide and Isoproterenol on Lipid Metabolism and Signaling in Primary Rat Adipocytes
Åkesson, L., Åhrén, B., Manganiello, V. C., Holst, L. S., Edgren, G., & Degerman, E. (2003) · Endocrinology · doi:10.1210/en.2003-0364 · Cited by 33 · see citing works
Effect of caloric restriction with or without n-3 polyunsaturated fatty acids on insulin sensitivity in obese subjects: a randomized placebo controlled trial
Razny, U., Kiec-Wilk, B., Polus, A., Goralska, J., Malczewska-Malec, M., Wnek, D., Zdzienicka, A., Gruca, A., Childs, C. E., Kapusta, M., et al. (2015) · BBA Clinical · doi:10.1016/j.bbacli.2015.05.001 · Cited by 27 · see citing works
The interplay of glucose-dependent insulinotropic polypeptide in adipose tissue
Kagdi, S., Lyons, S. A., & Beaudry, J. L. (2024) · Journal of Endocrinology · doi:10.1530/joe-23-0361 · Cited by 27 · see citing works
Analogs of Glucose-Dependent Insulinotropic Polypeptide With Increased Dipeptidyl Peptidase IV Resistance
Kühn‐Wache, K., Manhart, S., Hoffmann, T., Hinke, S. A., Gelling, R. W., Pederson, R. A., Mclntosh, C. H. S., & Demuth, H. U. (2006) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-46826-3_21 · Cited by 25 · see citing works
Self-citation
New physiological effects of the incretin hormones GLP-1 and GIP.
Asmar, M. (2011) · PubMed · Cited by 21 · see citing works
Cardiovascular biology of the GIP receptor
Greenwell, A. A., Chahade, J. J., & Ussher, J. R. (2019) · Peptides · doi:10.1016/j.peptides.2019.170228 · Cited by 21 · see citing works
PACAP support of neuronal survival requires MAPK- and activity-generated signals
Pugh, P. C., & Margiotta, J. F. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.11.012 · Cited by 21 · see citing works
Combined glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonism attenuates atherosclerosis severity in APOE*3-Leiden.CETP mice
van Eenige, R., Ying, Z., Tramper, N., Wiebing, V., Siraj, Z., de Boer, J. F., Lambooij, J. M., Guigas, B., Qu, H., Coşkun, T., et al. (2023) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2023.03.016 · Cited by 19 · see citing works
Regulation of energy metabolism through central GIPR signaling
Liśkiewicz, A., & Müller, T. D. (2024) · Peptides · doi:10.1016/j.peptides.2024.171198 · Cited by 17 · see citing works
Effects of gastric inhibitory polypeptide, somatostatin and epidermal growth factor on lipogenesis in ovine adipose explants
Baba, A. S., Harper, J. M. M., & BUTTERY, P. J. (2000) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/s0305-0491(00)00249-2 · Cited by 17 · see citing works
Resistin Knockout Mice Exhibit Impaired Adipocyte Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR) Expression
Kim, S., Nian, C., & McIntosh, C. H. S. (2012) · Diabetes · doi:10.2337/db12-0257 · Cited by 16 · see citing works
Self-citation
Adipose Tissue, at the Core of the Action of Incretin and Glucagon-Based Anti-Obesity Drugs
Villarroya, F., Peyrou, M., & Giralt, M. (2025) · Current Obesity Reports · doi:10.1007/s13679-025-00660-w · Cited by 14 · see citing works
Glucose-dependent Insulinotropic Polypeptide (GIP): Development of DP IV-Resistant Analogues with Therapeutic Potential
Hinke, S. A., Lynn, F. C., Ehses, J. A., Pamir, N., Manhart, S., Kühn‐Wache, K., Rosche, F., Demuth, H.-U., Pederson, R. A., & McIntosh, C. H. S. (2005) · Kluwer Academic Publishers eBooks · doi:10.1007/0-306-47920-6_35 · Cited by 14 · see citing works
Self-citation
Glucose‐dependent insulinotropic polypeptide induces lipolysis during stable basal insulin substitution and hyperglycaemia in men with type 1 diabetes: A randomized, double‐blind, placebo‐controlled, crossover clinical trial
Heimburger, S. M. N., Nielsen, C. N., Calanna, S., Holst, J. J., Vilsbøll, T., Knop, F. K., & Christensen, M. B. (2022) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14545 · Cited by 13 · see citing works
Individual and combined effects of GIP and xenin on differentiation, glucose uptake and lipolysis in 3T3-L1 adipocytes
English, A. R., Craig, S. L., Flatt, P. R., & Irwin, N. (2020) · Biological Chemistry · doi:10.1515/hsz-2020-0195 · Cited by 13 · see citing works
Pharmacological Advances in Incretin-Based Polyagonism: What We Know and What We Don’t
Novikoff, A., & Müller, T. D. (2024) · Physiology · doi:10.1152/physiol.00032.2023 · Cited by 13 · see citing works
Expression profiling identifies novel gene targets and functions forPdx1in the duodenum of mature mice
Chen, C., & Sibley, E. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00314.2011 · Cited by 12 · see citing works
Active Immunization with Glucose‐Dependent Insulinotropic Polypeptide Vaccine Influences Brain Function and Behaviour in Rats
Tian, J. ‐., Wang, Y., Lin, N., Guo, Y., Sun, S., & Zou, D.-C. (2010) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2010.02400.x · Cited by 11 · see citing works
Central Regulation of Glucose-Dependent Insulinotropic Polypeptide Secretion
Yavropoulou, M. P., & Yovos, J. G. (2010) · Vitamins and hormones · doi:10.1016/b978-0-12-381517-0.00006-0 · Cited by 10 · see citing works
Hormonal regulation of human adipose tissue lipolysis: impact of adipose GIP system in overweight and obesity
Brachs, S., Soll, D., Beer, F., Huckauf, N., Konkar, A. A., Spranger, J., Rütten, H., & Mai, K. (2025) · European Journal of Endocrinology · doi:10.1093/ejendo/lvae151 · Cited by 7 · see citing works
Molecular cloning, tissue distribution and functional characterization of glucose-dependent insulinotropic peptide (GIP) gene in Ctenopharyngodon idella
Yang, G., Liang, X., Qin, C., Yang, L., Zhang, Y., Lu, R., Yan, X., Meng, X., & Nie, G. (2021) · Aquaculture · doi:10.1016/j.aquaculture.2021.737682 · Cited by 6 · see citing works
Gastrointestinal Peptide Hormones Regulating Energy and Glucose Homeostasis
Drucker, D. J. (2006) · Elsevier eBooks · doi:10.1016/b978-012088394-3/50009-x · Cited by 4 · see citing works
The effects of a 12-week lifestyle intervention on incretin response during an oral glucose tolerance test in Latino youth with obesity and impaired glucose tolerance
Rosenberg, J., Williams, A. N., Gano, A., Deak, M. M., Shaibi, G. Q., & Kim, J. Y. (2025) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2025.109228 · Cited by 1 · see citing works
Beyond weight loss: How metabolism in human adipocytes is shaped by GLP-1R agonists and dual GIPR/GLP-1R agonists
Curto, R., Giglione, C., Cannarella, R., Berisha, H., Hattab, R., Condorelli, R. A., Vignera, S. L., Calogero, A. E., & Magni, P. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.108278 · Cited by 1 · see citing works
One receptor, two opposite approaches: efficacy and tolerability of GIPR agonism and antagonism in obesity pharmacotherapy
Gao, S., & Borner, T. (2026) · Appetite · doi:10.1016/j.appet.2026.108723 · Cited by 1 · see citing works
Glucose-Dependent Insulinotropic Polypeptide (GIP)
Kieffer, T. J. (2003) · Encyclopedia of Hormones · doi:10.1016/b0-12-341103-3/00123-6 · Cited by 1 · see citing works
Islet Amyloid Polypeptide/GLP‐1/Exendin
Baggio, L. L., & Drucker, D. J. (2003) · doi:10.1002/0470862092.d0209
A characterization of glucose-induced downregulation of the glucose dependent insulinotropic polypeptide receptor (GIPR)
Olver, A. (2011) · cIRcle (University of British Columbia) · doi:10.14288/1.0101080
The pro-survival effects of glucose-dependent insulinotropic polypeptide receptor signalling on beta cells
Widenmaier, S. B. (2010) · cIRcle (University of British Columbia) · doi:10.14288/1.0071070
Marine invertebrate and bacterial extract library screens for novel modulators of the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors
Merchant, C. E. (2011) · cIRcle (University of British Columbia) · doi:10.14288/1.0105089
A randomised controlled trial investigating the influences of food form and energy density on appetite, satiation and satiety in healthy adults
Carroll, S. (2014) · Queen Margaret University eTheses Repository
Role of leptin in the modulation of gustatory preference for fat in mice
Ullah, H. (2022) · doi:10.70675/dc2c226bz1561z4899zb6fez2f9ad7a488bf
Incretins: From Gene Expression to Secretion and Action of GLP-1 and GIP
Lobato, C. B., & Holst, J. J. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-11985-9.00004-4
Agonists and Antagonists of the Human GIP Receptor
Kizilkaya, H. S., Gasbjerg, L. S., Holst, J. J., & Rosenkilde, M. M. (2026) · doi:10.1002/9783527845408.ch2
DPP4 Substrate Supplementation Protects From WNT‐Induced Lipid Depletion in Dermal Adipocytes
Madhavan, S. R., Moore, P., Ma, Q., & Atit, R. P. (2026) · Experimental Dermatology · doi:10.1111/exd.70354
Adipocytes as a Mechanistic Link Between Incretin-Based Therapies and Hair Loss
Gupta, A. K., Kaur, J., Piguet, V., & Mirmirani, P. (2026) · Biology · doi:10.3390/biology15181642

Glucose-Dependent Insulinotropic Polypeptide Stimulation of Lipolysis in Differentiated 3T3-L1 Cells: Wortmannin-Sensitive Inhibition by Insulin
McIntosh, C. H. S. (1999) · Endocrinology · doi:10.1210/en.140.1.398 · Cited by 20 · see citing works
Self-citation
Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology 136
McIntosh, C. H. S., Bremsak, I. J., Lynn, F. C., Gill, R. E., Hinke, S. A., Gelling, R., Nian, C., Mcknight, G., Jaspers, S. R., Raymond, et al. (1995)
Self-citation
Functional GIP Receptors Are Present on Adipocytes
Yip, R. G.-C., Boylan, M. O., Kieffer, T. J., & Wolfe, M. M. (1998) · Endocrinology · doi:10.1210/endo.139.9.6288 · Cited by 237 · see citing works
Glucose-dependent insulinotropic polypeptide modulates adipocyte lipolysis and reesterification
Getty‐Kaushik, L., Song, D. H., Boylan, M. O., Corkey, B. E., & Wolfe, M. M. (2006) · Obesity · doi:10.1038/oby.2006.129 · Cited by 134 · see citing works
Activation of Lipoprotein Lipase by Glucose-dependent Insulinotropic Polypeptide in Adipocytes
Kim, S.-J., Nian, C., & McIntosh, C. H. S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609088200 · Cited by 216 · see citing works
Self-citation

Authors: McIntosh, C. H. S., Bremsak, I., Lynn, F. C., Gill, R., Hinke, S. A., Gelling, R., Nian, C., McKnight, G., Jaspers, S., & Pederson, R. A.
Affiliations: University of British Columbia (CA)
Department of Zymogenetics, Inc. (G.M., S.J.), Seattle, Washington
Corresponding author: McIntosh, Christopher H. S.
ORCID: Lynn, Francis C.
Hinke, Simon A.
Gelling, Richard
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 1999-01-01
Volume: 140
Issue: 1
Pages: 398-404
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/endo.140.1.6464
OpenAlex: W2001123714
Cited by: 73
References: 49
Citations by year: 2026: 6 · 2025: 4 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 6 · 2018: 1 · 2015: 1 · 2014: 1 · 2012: 7
FWCI: 0.67
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Diabetes Association
Medical Research Council Canada
Medical Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: glucose-dependent insulinotropic polypeptide, lipolysis, adipocytes, 3T3-L1 cells, GIP receptor, insulin antagonism, wortmannin, phosphatidylinositol 3-kinase, cAMP signaling, glycerol release, fat metabolism
MeSH terms: Adenylyl Cyclase Inhibitors, Wortmannin, Cyclic AMP, Androstadienes, Animals, Cell Differentiation, Gastric Inhibitory Polypeptide, Insulin, Insulin Antagonists, Lipolysis, Receptors, Gastrointestinal Hormone, RNA, Messenger, 3T3 Cells, Mice

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