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Individual and combined effects of GIP and xenin on differentiation, glucose uptake and lipolysis in 3T3-L1 adipocytes

  • Andrew English , Sarah L. Craig , Peter R. Flatt and Nigel Irwin EMAIL logo
Published/Copyright: August 26, 2020
Biological Chemistry
From the journal Biological Chemistry Volume 401 Issue 11

Abstract

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP), released postprandially from K-cells, has established actions on adipocytes and lipid metabolism. In addition, xenin, a related peptide hormone also secreted from K-cells after a meal, has postulated effects on energy regulation and lipid turnover. The current study has probed direct individual and combined effects of GIP and xenin on adipocyte function in 3T3-L1 adipocytes, using enzyme-resistant peptide analogues, (d-Ala2)GIP and xenin-25-Gln, and knockdown (KD) of receptors for both peptides. (d-Ala2)GIP stimulated adipocyte differentiation and lipid accumulation in 3T3-L1 adipocytes over 96 h, with xenin-25-Gln evoking similar effects. Combined treatment significantly countered these individual adipogenic effects. Individual receptor KD impaired lipid accumulation and adipocyte differentiation, with combined receptor KD preventing differentiation. (d-Ala2)GIP and xenin-25-Gln increased glycerol release from 3T3-L1 adipocytes, but this lipolytic effect was significantly less apparent with combined treatment. Key adipogenic and lipolytic genes were upregulated by (d-Ala2)GIP or xenin-25-Gln, but not by dual peptide culture. Similarly, both (d-Ala2)GIP and xenin-25-Gln stimulated insulin-induced glucose uptake in 3T3-L1 adipocytes, but this effect was annulled by dual treatment. In conclusion, GIP and xenin possess direct, comparable, lipogenic and lipolytic actions in 3T3-L1 adipocytes. However, effects on lipid metabolism are significantly diminished by combined administration.

Keywords: 3T3-L1 adipocytes; differentiation; glucose-dependent insulinotropic polypeptide (GIP); glucose uptake; lipid metabolism; xenin
Corresponding author: Nigel Irwin, SAAD Centre for Pharmacy and Diabetes, Ulster University, Coleraine, Northern Ireland, UK, E-mail:

Funding source: Invest Northern Ireland

Award Identifier / Grant number: Proof of Concept funding

Funding source: European Foundation for the Study of Diabetes

Award Identifier / Grant number: EFSD/Lilly European Diabetes Research Programme 2017

Funding source: Department for the Economy, Northern Ireland

Award Identifier / Grant number: PhD studentship (SLC)

Acknowledgments

These studies were supported by research grants from Invest Northern Ireland Proof of Concept funding, European Foundation for the Study of Diabetes and Department for the Economy, Northern Ireland.

  1. Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: These studies were supported by research grants from Invest Northern Ireland Proof of Concept funding, European Foundation for the Study of Diabetes and Department for the Economy, Northern Ireland.

  3. Conflict of interest statement: All authors declare no conflict of interest.

References

Alexiou, C., Zimmermann, J., Schick, R., and Schusdziarra, V. (1998). Xenin—a novel suppressor of food intake in rats. Brain Res 800: 294–299, https://doi.org/10.1016/s0006-8993(98)00535-6.Search in Google Scholar

Althage, M.C., Ford, E.L., Wang, S., Tso, P., Polonsky, K.S., and Wice, B.M. (2008). Targeted ablation of GIP-producing cells in transgenic mice reduces obesity and insulin resistance induced by a high fat diet. J. Biol. Chem. 27: 18365–18376, https://doi.org/10.1074/jbc.m710466200.Search in Google Scholar

Baldassano, S., Gasbjerg, L.S., Kizilkaya, H.S., Rosenkilde, M.M., Holst, J.J., and Hartmann, B. (2019). Increased body weight and fat mass after subchronic GIP receptor antagonist, but not GLP-2 receptor antagonist, administration in rats. Front. Endocrinol. 10: 492, https://doi.org/10.3389/fendo.2019.00492.Search in Google Scholar

Bhavya, S., San Lew, P., and Mizuno, T.M. (2017). Central action of xenin affects the expression of lipid metabolism-related genes and proteins in mouse white adipose tissue. Neuropeptides 63: 67–73, https://doi.org/10.1016/j.npep.2017.01.007.Search in Google Scholar

Bhavya, S., San Lew, P., and Mizuno, T.M. (2018). Stimulation of white adipose tissue lipolysis by xenin, a neurotensin-related peptide. Biochem. Biophys. Res. Commun. 498: 842–848, https://doi.org/10.1016/j.bbrc.2018.03.067.Search in Google Scholar

Boylan, M.O., Glazebrook, P.A., Tatalovic, M., and Wolfe, M. (2015). Su2066 immunoneutralization of gastric inhibitory polypeptide (GIP) attenuates weight gain in mice. Gastroenterology 148: 588–589, https://doi.org/10.1016/s0016-5085(15)31995-8.Search in Google Scholar

Ceperuelo-Mallafré, V., Duran, X., Pachón, G., Roche, K., Garrido-Sánchez, L., Vilarrasa, N., Tinahones, F.J., Vicente, V., Pujol, J., and Vendrell, J. (2014). Disruption of GIP/GIPR axis in human adipose tissue is linked to obesity and insulin resistance. J. Clin. Endocrinol. Metab. 99: 908–919, https://doi.org/10.1210/jc.2013-3350.Search in Google Scholar PubMed

Chen, J., Zhao, H., Ma, X., Zhang, Y., Lu, S., Wang, Y., Zong, C., Qin, D., Wang, Y., Yang, Y.Y., et al. (2017). GLP-1/GLP-1R signaling in regulation of adipocyte differentiation and lipogenesis. Cell. Physiol. Biochem. 42: 1165–1176, https://doi.org/10.1159/000478872.Search in Google Scholar PubMed

Chowdhury, S., Wang, S., Patterson, B.W., Reeds, D.N., and Wice, B.M. (2013). The combination of GIP plus xenin-25 indirectly increases pancreatic polypeptide release in humans with and without type 2 diabetes mellitus. Regul. Pept. 187: 42–50, https://doi.org/10.1016/j.regpep.2013.10.003.Search in Google Scholar PubMed PubMed Central

Cooke, J.H., Patterson, M., Patel, S.R., Smith, K.L., Ghatei, M.A., Bloom, S.R., and Murphy, K.G. (2009). Peripheral and central administration of xenin and neurotensin suppress food intake in rodents. Obesity 17: 1135–1143. https://doi.org/10.1038/oby.2008.652.Search in Google Scholar PubMed

Craig, S., Perry, R., Vyavahare, S., Ng, M., Gault, V.A., Flatt, P.R., and Irwin, N. (2020). A GIP/xenin hybrid in combination with exendin-4 improves metabolic status in db/db diabetic mice and promotes enduring antidiabetic benefits in high fat fed mice. Biochem. Pharmacol. 171: 113723, https://doi.org/10.1016/j.bcp.2019.113723.Search in Google Scholar

Craig, S.L., Gault, V.A., and Irwin, N. (2018). Emerging therapeutic potential for xenin and related peptides in obesity and diabetes. Diabetes. Metab. Res. Rev. 34: 3006, https://doi.org/10.1002/dmrr.3006.Search in Google Scholar

Creutzfeldt, W., Ebert, R., Willms, B., Frerichs, H., and Brown, J. (1978). Gastric inhibitory polypeptide (GIP) and insulin in obesity: increased response to stimulation and defective feedback control of serum levels. Diabetologia 14: 15–24, https://doi.org/10.1007/bf00429703.Search in Google Scholar

English, A. and Irwin, N. (2019). Nonclassical islet peptides: pancreatic and extrapancreatic actions. Clin. Med. Insights Endocrinol. Diabetes 12: 1179551419888871, https://doi.org/10.1177/1179551419888871.Search in Google Scholar

Feurle, G.E., Hamscher, G., Kusiek, R., Meyer, H., and Metzger, J. (1992). Identification of xenin, a xenopsin-related peptide, in the human gastric mucosa and its effect on exocrine pancreatic secretion. J. Biol. Chem. 267: 22305–22309.10.1016/S0021-9258(18)41670-5Search in Google Scholar

Gault, V., Parker, J., Harriott, P., Flatt, P., and O’Harte, F. (2002). Evidence that the major degradation product of glucose-dependent insulinotropic polypeptide, GIP (3–42), is a GIP receptor antagonist in vivo. J. Endocrinol. 175: 525–534, https://doi.org/10.1677/joe.0.1750525.Search in Google Scholar

Gault, V.A., Irwin, N., Green, B.D., McCluskey, J.T., Greer, B., Bailey, C.J., Harriott, P., O’Harte, F.P., and Flatt, P.R. (2005). Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3) GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-related diabetes. Diabetes 54: 2436–2446, https://doi.org/10.2337/diabetes.54.8.2436.Search in Google Scholar

Gault, V.A., Martin, C., Flatt, P.R., Parthsarathy, V., and Irwin, N. (2015). Xenin-25 [Lys 13 PAL]: a novel long-acting acylated analogue of xenin-25 with promising antidiabetic potential. Acta Diabetol. 52: 461–471, https://doi.org/10.1007/s00592-014-0681-0.Search in Google Scholar

Getty‐Kaushik, L., Song, D.H., Boylan, M.O., Corkey, B.E., and Wolfe, M.M. (2006). Glucose‐dependent insulinotropic polypeptide modulates adipocyte lipolysis and reesterification. Obesity 14: 1124–1131.10.1038/oby.2006.129Search in Google Scholar

Gliemann, J., Gammeltoft, S., and Vinten, J. (1975). Time course of insulin-receptor binding and insulin-induced lipogenesis in isolated rat fat cells. J. Biol. Chem. 250: 3368–3374.10.1016/S0021-9258(19)41524-XSearch in Google Scholar

Gobron, B., Bouvard, B., Vyavahare, S., Blom, L., Pedersen, K., Windeløv, J., Boer, G., Harada, N., Zhang, S., Shimazu‐Kuwahara, S., et al. (2020). Enteroendocrine K‐cells exert complementary effects to control bone quality and mass in mice. J. Bone Miner. Res. 35: 1363–1374, https://doi.org/10.1002/jbmr.4004.Search in Google Scholar PubMed

Gonzales, A.M., and Orlando, R.A. (2007). Role of adipocyte-derived lipoprotein lipase in adipocyte hypertrophy. Nutr. Metab. 4: 22, https://doi.org/10.1186/1743-7075-4-22.Search in Google Scholar PubMed PubMed Central

Greenfield, J.R., Farooqi, I.S., Keogh, J.M., Henning, E., Habib, A.M., Blackwood, A., Reimann, F., Holst, J.J., and Gribble, F.M. (2009). Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. Am. J. Clin. Nutr. 89: 106–113, https://doi.org/10.3945/ajcn.2008.26362.Search in Google Scholar PubMed PubMed Central

Hallberg, M. (2015). Neuropeptides: metabolism to bioactive fragments and the pharmacology of their receptors. Med. Res. Rev. 35: 464–519, https://doi.org/10.1002/med.21323.Search in Google Scholar PubMed

Hasib, A., Ng, M.T., Gault, V.A., Khan, D., Parthsarathy, V., Flatt, P.R., and Irwin, N. (2017). An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice. Diabetologia 60: 541–552, https://doi.org/10.1007/s00125-016-4186-y.Search in Google Scholar PubMed PubMed Central

Hauner, H., Glatting, G., Kaminska, D., and Pfeiffer, E.F. (1988). Effects of gastric inhibitory polypeptide on glucose and lipid metabolism of isolated rat adipocytes. Ann Nutr Metab 32: 282–288, https://doi.org/10.1159/000177467.Search in Google Scholar PubMed

Irwin, N. and Flatt, P.R. (2009). Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications. Diabetologia 52: 1724–1731, https://doi.org/10.1007/s00125-009-1422-8.Search in Google Scholar PubMed

Irwin, N., McClean, P., O’Harte, F., Gault, V., Harriott, P., and Flatt, P.R. (2007). Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro 3) GIP prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice. Diabetologia 50: 1532–1540, https://doi.org/10.1007/s00125-007-0692-2.Search in Google Scholar PubMed

Irwin, N., Flatt, P.R., and Gault, V.A. (2008). GIP-based therapeutics for diabetes and obesity. Curr. Chem. Biol. 2: 60–67, https://doi.org/10.2174/187231308783334108.Search in Google Scholar

Irwin, N., Francis, J.M., and Flatt, P.R. (2011). Insulin modulates glucose-dependent insulinotropic polypeptide (GIP) secretion from enteroendocrine K cells in rats. Biol. Chem. 392: 909–918, https://doi.org/10.1515/bc.2011.176.Search in Google Scholar PubMed

Kim, S.J., Nian, C., and McIntosh, C.H. (2010). GIP increases human adipocyte LPL expression through CREB and TORC2-mediated trans-activation of the LPL gene. J. Lipid Res. 51: 3145–3157, https://doi.org/10.1194/jlr.m006841.Search in Google Scholar

Koon, H.W., Kim, Y.S., Xu, H., Kumar, A., Zhao, D., Karagiannides, I., Dobner, P.R.,and Pothoulakis, C. (2009). Neurotensin induces IL-6 secretion in mouse preadipocytes and adipose tissues during 2, 4, 6,-trinitrobenzensulphonic acid-induced colitis. In Proceedings of the national academy of science of the United States of America, vol. 106. pp. 8766–8771. Boston: National Academy of Sciences. https://doi.org/10.1073/pnas.0903499106.Search in Google Scholar

Li, J., Song, J., Weiss, H.L., Weiss, T., Townsend, C.M.Jr., and Evers, B.M. (2016a). Activation of AMPK stimulates neurotensin secretion in neuroendocrine cells. Mol. Endocrinol. 30: 26–36, https://doi.org/10.1210/me.2015-1094.Search in Google Scholar

Li, J., Song, J., Zaytseva, Y.Y., Liu, Y., Rychahou, P., Jiang, K., Starr, M.E., Kim, J.T., Harris, J.W., and Yiannikouris, F.B. (2016b). An obligatory role for neurotensin in high-fat-diet-induced obesity. Nature 533: 411–415, https://doi.org/10.1038/nature17662.Search in Google Scholar

Maiuri, T., Ho, J., and Stambolic, V. (2010). Regulation of adipocyte differentiation by distinct subcellular pools of protein kinase B (PKB/Akt). J. Biol. Chem. 285: 15038–15047, https://doi.org/10.1074/jbc.m110.121434.Search in Google Scholar

Mannaerts, G.P., Van Veldhoven, P.P., and Casteels, M. (2000). Peroxisomal lipid degradation via β-and α-oxidation in mammals. Cell Biochem. Biophys. 32: 73–87, https://doi.org/10.1385/cbb:32:1-3:73.10.1385/CBB:32:1-3:73Search in Google Scholar

Manning, B.D., and Toker, A. (2017). AKT/PKB signaling: navigating the network. Cell 169: 381–405, https://doi.org/10.1016/j.cell.2017.04.001.Search in Google Scholar PubMed PubMed Central

Martin, C.M., Gault, V.A., McClean, S., Flatt, P.R., and Irwin, N. (2012). Degradation, insulin secretion, glucose-lowering and GIP additive actions of a palmitate-derivatised analogue of xenin-25. Biochem. Pharmacol. 84: 312–319, https://doi.org/10.1016/j.bcp.2012.04.015.Search in Google Scholar PubMed

Martin, C.M., Irwin, N., Flatt, P.R., and Gault, V.A. (2013). A novel acylated form of (D-Ala2) GIP with improved antidiabetic potential, lacking effect on body fat stores. Biochim. Biophys. Acta Gen. Subj. 1830: 3407–3413, https://doi.org/10.1016/j.bbagen.2013.03.011.Search in Google Scholar PubMed

Martin, C.M., Parthsarathy, V., Pathak, V., Gault, V.A., Flatt, P.R., and Irwin, N. (2014). Characterisation of the biological activity of xenin-25 degradation fragment peptides. J. Endocrinol. 221: 193–200, https://doi.org/10.1530/joe-13-0617.Search in Google Scholar PubMed

Martin, C.M., Parthsarathy, V., Hasib, A., Ng, M.T., McClean, S., Flatt, P.R., Gault, V.A., and Irwin, N. (2016). Biological activity and antidiabetic potential of C-terminal octapeptide fragments of the gut-derived hormone xenin. PloS One 11: e0152818, https://doi.org/10.1371/journal.pone.0152818.Search in Google Scholar

McClean, P., Gault, V., Irwin, N., McCluskey, J.T., and Flatt, P.R. (2008). Daily administration of the GIP‐R antagonist (Pro3) GIP in streptozotocin‐induced diabetes suggests that insulin‐dependent mechanisms are critical to anti–obesity‐diabetes actions of (Pro3) GIP. Diabetes Obes. Metab. 10: 336–342, https://doi.org/10.1111/j.1463-1326.2007.00712.x.Search in Google Scholar

McIntosh, C.H., Bremsak, I., Lynn, F.C., Gill, R., Hinke, S.A., Gelling, R., Nian, C., McKnight, G., Jaspers, S., and Pederson, R.A. (1999). Glucose-dependent insulinotropic polypeptide stimulation of lipolysis in differentiated 3T3-L1 cells: wortmannin-sensitive inhibition by insulin. Endocrinology 140: 398–404, https://doi.org/10.1210/endo.140.1.6464.Search in Google Scholar

Mitchell, J., Jacobsson, A., Kirchgessner, T.G., Schotz, M.C., Cannon, B., and Nedergaard, J. (1992). Regulation of expression of the lipoprotein lipase gene in brown adipose tissue. Am. J. Physiol. 263: 500–506, https://doi.org/10.1152/ajpendo.1992.263.3.e500.Search in Google Scholar

Mohammad, S., Ramos, L.S., Buck, J., Levin, L.R., Rubino, F., and McGraw, T.E. (2011). Gastric inhibitory peptide controls adipose insulin sensitivity via activation of cAMP-response element-binding protein and p110beta isoform of phosphatidylinositol 3-kinase. J Biol Chem 286: 43062–43070, https://doi.org/10.1074/jbc.m111.289009.Search in Google Scholar

Moustaid, N. and Sul, H.S. (1991). Regulation of expression of the fatty acid synthase gene in 3T3-L1 cells by differentiation and triiodothyronine. J. Biol. Chem. 266: 18550–18554.10.1016/S0021-9258(18)55097-3Search in Google Scholar

Mroz, P.A., Finan, B., Gelfanov, V., Yang, B., Tschöp, M.H., DiMarchi, R.D., and Perez-Tilve, D. (2019). Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism. Mol. Metab 20: 51–62, https://doi.org/10.1016/j.molmet.2018.12.001.Search in Google Scholar

Nasteska, D., Harada, N., Suzuki, K., Yamane, S., Hamasaki, A., Joo, E., Iwasaki, K., Shibue, K., Harada, T., and Inagaki, N. (2014). Chronic reduction of GIP secretion alleviates obesity and insulin resistance under high-fat diet conditions. Diabetes 63: 2332–2343, https://doi.org/10.2337/db13-1563.Search in Google Scholar

Nogalska, A., and Swierczynski, J. (2001). The age-related differences in obese and fatty acid synthase gene expression in white adipose tissue of rat. Biochim. Biophys. Acta 1533: 73–80, https://doi.org/10.1016/s1388-1981(01)00142-1.Search in Google Scholar

Parthsarathy, V., Irwin, N., Hasib, A., Martin, C.M., McClean, S., Bhat, V.K., Ng, M.T., Flatt, P.R., and Gault, V.A. (2016). A novel chemically modified analogue of xenin-25 exhibits improved glucose-lowering and insulin-releasing properties. Biochim. Biophys. Acta Gen. Subj. 1860: 757–764, https://doi.org/10.1016/j.bbagen.2016.01.015.Search in Google Scholar PubMed

Piatek, J., Mackowiak, P., Krauss, H., Nowak, D., and Bogdanski, P. (2011). In vivo investigations of neurotensin receptors in adipocytes, hepatocytes and enterocytes of rat. Ann. Agric. Environ. Med. 18: 433–436.Search in Google Scholar

Salazar, M.R., Carbajal, H.A., Espeche, W.G., Dulbecco, C.A., Aizpurúa, M., Marillet, A.G., Echeverría, R.F., and Reaven, G.M. (2011). Relationships among insulin resistance, obesity, diagnosis of the metabolic syndrome and cardio-metabolic risk. Diabetes Vasc. Dis. Res. 8: 109–116, https://doi.org/10.1177/1479164111403170.Search in Google Scholar

Saponaro, C., Gaggini, M., Carli, F., and Gastaldelli, A. (2015). The subtle balance between lipolysis and lipogenesis: a critical point in metabolic homeostasis. Nutrients 7: 9453–9474, https://doi.org/10.3390/nu7115475.Search in Google Scholar

Semenkovich, C., Wims, M., Noe, L., Etienne, J., and Chan, L. (1989). Insulin regulation of lipoprotein lipase activity in 3T3-L1 adipocytes is mediated at posttranscriptional and posttranslational levels. J. Biol. Chem. 264: 9030–9038.10.1016/S0021-9258(18)81898-1Search in Google Scholar

Shan, T., Liu, J., Wu, W., Xu, Z., and Wang, Y. (2017). Roles of notch signaling in adipocyte progenitor cells and mature adipocytes. J. Cell. Physiol. 232: 1258–1261, https://doi.org/10.1002/jcp.25697.Search in Google Scholar PubMed

Song, D.H., Getty–Kaushik, L., Tseng, E., Simon, J., Corkey, B.E., and Wolfe, M.M. (2007). Glucose-dependent insulinotropic polypeptide enhances adipocyte development and glucose uptake in part through Akt activation. Gastroenterology 133: 1796–1805, https://doi.org/10.1053/j.gastro.2007.09.005.Search in Google Scholar PubMed PubMed Central

Sparre-Ulrich, A., Gabe, M., Gasbjerg, L., Christiansen, C., Svendsen, B., Hartmann, B., Holst, J., and Rosenkilde, M. (2017). GIP (3–30) NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release. Biochem. Pharmacol. 131: 78–88, https://doi.org/10.1016/j.bcp.2017.02.012.Search in Google Scholar PubMed

Starich, G.H., Bar, R.S., and Mazzaferri, E.L. (1985). GIP increases insulin receptor affinity and cellular sensitivity in adipocytes. Am. J. Physiol. Endocrinol. Metab. 249: 603–607, https://doi.org/10.1152/ajpendo.1985.249.6.e603.Search in Google Scholar PubMed

Szalowska, E., Meijer, K., Kloosterhuis, N., Razaee, F., Priebe, M., and Vonk, R.J. (2011). Sub-chronic administration of stable GIP analog in mice decreases serum LPL activity and body weight. Peptides 32: 938–945, https://doi.org/10.1016/j.peptides.2011.02.011.Search in Google Scholar PubMed

Sztalryd, C., Komaromy, M.C., and Kraemer, F.B. (1995). Overexpression of hormone-sensitive lipase prevents triglyceride accumulation in adipocytes. J. Clin. Invest. 95: 2652–2661, https://doi.org/10.1172/jci117967.Search in Google Scholar

Taylor, A.I., Irwin, N., McKillop, A.M., Patterson, S., Flatt, P.R., and Gault, V.A. (2010). Evaluation of the degradation and metabolic effects of the gut peptide xenin on insulin secretion, glycaemic control and satiety. J. Endocrinol. 207: 87–93, https://doi.org/10.1677/joe-10-0085.Search in Google Scholar

Thomsen, C., Rasmussen, O., Lousen, T., Holst, J.J., Fenselau, S., Schrezenmeir, J., and Hermansen, K. (1999). Differential effects of saturated and monounsaturated fatty acids on postprandial lipemia and incretin responses in healthy subjects. Am. J. Clin. Nutr. 69: 1135–1143, https://doi.org/10.1093/ajcn/69.6.1135.Search in Google Scholar PubMed

Wice, B.M., Wang, S., Crimmins, D.L., Diggs-Andrews, K.A., Althage, M.C., Ford, E.L., Tran, H., Ohlendorf, M., Griest, T.A., Wang, Q., et al. (2010). Xenin-25 potentiates glucose-dependent insulinotropic polypeptide action via a novel cholinergic relay mechanism. J. Biol. Chem. 285: 19842–19853, https://doi.org/10.1074/jbc.m110.129304.Search in Google Scholar

Wice, B.M., Reeds, D.N., Tran, H.D., Crimmins, D.L., Patterson, B.W., Dunai, J., Wallendorf, M.J., Ladenson, J.H., Villareal, D.T., and Polonsky, K.S. (2012). Xenin-25 amplifies GIP-mediated insulin secretion in humans with normal and impaired glucose tolerance but not type 2 diabetes. Diabetes 61: 1793–1800, https://doi.org/10.2337/db11-1451.Search in Google Scholar PubMed PubMed Central

Yip, R.G., Boylan, M.O., Kieffer, T.J., and Wolfe, M.M. (1998). Functional GIP receptors are present on adipocytes. Endocrinology 139: 4004–4007, https://doi.org/10.1210/endo.139.9.6288.Search in Google Scholar PubMed

Received: 2020-05-22
Accepted: 2020-08-04
Published Online: 2020-08-26
Published in Print: 2020-10-25

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/hsz-2020-0195
Keywords for this article
3T3-L1 adipocytes; differentiation; glucose-dependent insulinotropic polypeptide (GIP); glucose uptake; lipid metabolism; xenin

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. The role of mitochondrial ATP synthase in cancer
  4. Redox-dependent and independent effects of thioredoxin interacting protein
  5. Hsp70-mediated quality control: should I stay or should I go?
  6. Research articles/Short communications
  7. Protein structure and function
  8. Insights on intermolecular FMN-heme domain interaction and the role of linker length in cytochrome P450cin fusion proteins
  9. Cell biology and signaling
  10. Zinc-dependent changes in oxidative and endoplasmic reticulum stress during cardiomyocyte hypoxia/reoxygenation
  11. Histone deacetylase 1 regulates the malignancy of oral cancer cells via miR-154-5p/PCNA axis
  12. The impact of oxytocin on thiol/disulphide and malonyldialdehyde/glutathione homeostasis in stressed rats
  13. Individual and combined effects of GIP and xenin on differentiation, glucose uptake and lipolysis in 3T3-L1 adipocytes
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