G-protein-coupled receptor 40 agonist GW9508 potentiates glucose-stimulated insulin secretion through activation of protein kinase Cα and ε in INS-1 cells
Autoři:
Takuya Hashimoto aff001; Hideo Mogami aff002; Daisuke Tsuriya aff001; Hiroshi Morita aff001; Shigekazu Sasaki aff001; Tatsuro Kumada aff003; Yuko Suzuki aff004; Tetsumei Urano aff004; Yutaka Oki aff001; Takafumi Suda aff001
Působiště autorů:
2nd Department of Internal Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
aff001; Department of Health and Nutrition, Tokoha University, Shizuoka, Japan
aff002; Department of Occupational Therapy, Tokoha University, Shizuoka, Japan
aff003; Department of Medical Physiology, Hamamatsu University School of Medicine, Shizuoka, Japan
aff004; Department of Family and Community Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan
aff005
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0222179
Souhrn
Objective
The mechanism by which G-protein-coupled receptor 40 (GPR40) signaling amplifies glucose-stimulated insulin secretion through activation of protein kinase C (PKC) is unknown. We examined whether a GPR40 agonist, GW9508, could stimulate conventional and novel isoforms of PKC at two glucose concentrations (3 mM and 20 mM) in INS-1D cells.
Methods
Using epifluorescence microscopy, we monitored relative changes in the cytosolic fluorescence intensity of Fura2 as a marker of change in intracellular Ca2+ ([Ca2+]i) and relative increases in green fluorescent protein (GFP)-tagged myristoylated alanine-rich C kinase substrate (MARCKS-GFP) as a marker of PKC activation in response to GW9508 at 3 mM and 20 mM glucose. To assess the activation of the two PKC isoforms, relative increases in membrane fluorescence intensity of PKCα-GFP and PKCε-GFP were measured by total internal reflection fluorescence microscopy. Specific inhibitors of each PKC isotype were constructed and synthesized as peptide fusions with the third α-helix of the homeodomain of Antennapedia.
Results
At 3 mM glucose, GW9508 induced sustained MARCKS-GFP translocation to the cytosol, irrespective of changes in [Ca2+]i. At 20 mM glucose, GW9508 induced sustained MARCKS-GFP translocation but also transient translocation that followed sharp increases in [Ca2+]i. Although PKCα translocation was rarely observed, PKCε translocation to the plasma membrane was sustained by GW9508 at 3 mM glucose. At 20 mM glucose, GW9508 induced transient translocation of PKCα and sustained translocation as well as transient translocation of PKCε. While the inhibitors (75 μM) of each PKC isotype reduced GW9508-potentiated, glucose-stimulated insulin secretion in INS-1D cells, the PKCε inhibitor had a more potent effect.
Conclusion
GW9508 activated PKCε but not PKCα at a substimulatory concentration of glucose. Both PKC isotypes were activated at a stimulatory concentration of glucose and contributed to glucose-stimulated insulin secretion in insulin-producing cells.
Klíčová slova:
Biology and life sciences – Cell biology – Biochemistry – Physical sciences – Chemistry – Research and analysis methods – Medicine and health sciences – Chemical compounds – Cellular structures and organelles – Physiology – Organic compounds – Carbohydrates – Monosaccharides – Organic chemistry – Endocrinology – Diabetic endocrinology – Insulin – Hormones – Cell membranes – Imaging techniques – Endocrine physiology – Signal transduction – Glucose – Insulin secretion – Cell signaling – Glucose signaling – Cytosol – Microscopy – Light microscopy – Fluorescence microscopy – Fluorescence imaging
Zdroje
1. Guariguata L, Whiting DR, Hambleton I, Beagley J. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. Elsevier Ireland Ltd; 2014;103: 137–149. doi: 10.1016/j.diabres.2013.11.002 24630390
2. Prentki M, Nolan CJ. Islet beta cell failure in type 2 diabetes. J Clin Invest. 2006;116: 1802–1812. doi: 10.1172/JCI29103 16823478
3. Newsholme P, Gaudel C MN. Nutrient regulation of insulin secretion and beta-cell functional integrity. Adv Exp Med Biol. 2010;654: 91–114. doi: 10.1007/978-90-481-3271-3_6 20217496
4. Drucker DJ. Incretin action in the pancreas: Potential promise, possible perils, and pathological pitfalls. Diabetes. 2013;62: 3316–3323. doi: 10.2337/db13-0822 23818527
5. Ahrén B. Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes. Nat Rev Drug Discov. 2009;8: 369–385. doi: 10.1038/nrd2782 19365392
6. Holz GG. Epac: A New cAMP-Binding Protein in Support of Glucagon-like Peptide-1 Receptor-Mediated Signal Transduction in the Pancreatic β-Cell. Diabetes. 2004;53: 5–13. doi: 10.2337/diabetes.53.1.5 14693691
7. Suzuki Y, Zhang H, Saito N, Kojima I, Urano T, Mogami H. Glucagon-like peptide 1 activates protein kinase C through Ca2+-dependent activation of phospholipase C in insulin-secreting cells. J Biol Chem. 2006;281: 28499–28507. doi: 10.1074/jbc.M604291200 16870611
8. Shigeto M, Ramracheya R, Tarasov AI, Cha CY, Chibalina M V, Hastoy B, et al. GLP-1 stimulates insulin secretion by PKC-dependent TRPM4 and TRPM5 activation. J Clin Invest. 2015;125: 4714–4728. doi: 10.1172/JCI81975 26571400
9. Mellor H, Parker PJ. The extended protein kinase C superfamily. Biochem J. 1998;332: 281–292. doi: 10.1042/bj3320281 9601053
10. Rayasam GV, Tulasi VK, Davis JA BV. Fatty acid receptors as new therapeutic targets for diabetes. Expert Opin Ther Targets. 2007;11: 661–671. doi: 10.1517/14728222.11.5.661 17465724
11. Milligan G, Stoddart LA, Brown AJ. G protein-coupled receptors for free fatty acids. Cell Signal. 2006;18: 1360–1365. doi: 10.1016/j.cellsig.2006.03.011 16716567
12. Stoddart LA, Smith NJ, Milligan G. International Union of Pharmacology. LXXI. Free fatty acid receptors FFA1, -2, and -3: pharmacology and pathophysiological functions. Pharmacol Rev. 2008;60: 405–417. doi: 10.1124/pr.108.00802 19047536
13. Fujiwara K, Maekawa F, Yada T, Maekawa F, Oleic TY, Chain L, et al. Oleic acid interacts with GPR40 to induce Ca2+ signaling in rat islet beta-cells: mediation by PLC and L-type Ca2+ channel and link to insulin release. Am J Physiol Endocrinol Metab. 2005;289: E670–E677. doi: 10.1152/ajpendo.00035.2005 15914509
14. MJ B, RF. I. Inositol phosphates and cell signalling. Nature. 1989;341: 197–205. doi: 10.1038/341197a0 2550825
15. Itoh Y, Kawamata Y, Harada M, Kobayashi M, Fujii R, Fukusumi S, et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature. 2003;422: 173–176. doi: 10.1038/nature01478 12629551
16. Briscoe CP, Tadayyon M, Andrews JL, Benson WG, Chambers JK, Eilert MM, et al. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J Biol Chem. 2003;278: 11303–11311. doi: 10.1074/jbc.M211495200 12496284
17. Tomita T, Masuzaki H, Iwakura H, Fujikura J, Noguchi M, Tanaka T, et al. Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insulin secretion. Diabetologia. 2006;49: 962–968. doi: 10.1007/s00125-006-0193-8 16525841
18. Tomita T, Masuzaki H, Noguchi M, Iwakura H, Fujikura J, Tanaka T, et al. GPR40 gene expression in human pancreas and insulinoma. Biochem Biophys Res Commun. 2005;338: 1788–1790. doi: 10.1016/j.bbrc.2005.10.161 16289108
19. Latour MG, Alquier T, Oseid E, Tremblay C, Thomas L, Luo J, et al. GPR40 is necessary but not sufficient for fatty acid stimulation of insulin secretion in vivo. Diabetes. 2007;56: 1087–1094. doi: 10.2337/db06-1532 17395749
20. Tan CP, Feng Y, Zhou Y, Eiermann GJ, Petrov A, Zhou C, et al. Selective small-molecule agonists of G protein-coupled receptor 40 promote glucose-dependent insulin secretion and reduce blood glucose in mice. Diabetes. 2008;57: 2211–2219. doi: 10.2337/db08-0130 18477808
21. Briscoe CP, Peat AJ, Mckeown SC, Corbett DF, Goetz AS, Littleton TR, et al. Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Br J Pharmacol. 2006;148: 619–628. doi: 10.1038/sj.bjp.0706770 16702987
22. Salehi A, Flodgren E, Nilsson NE, Jimenez-Feltstrom J, Miyazaki J, Owman C OB. Free fatty acid receptor 1 (FFA(1)R/GPR40) and its involvement in fatty-acid-stimulated insulin secretion. Cell Tissue Res. 2005;322: 207–215. doi: 10.1007/s00441-005-0017-z 16044321
23. Shapiro H, Shachar S, Sekler I, Hershfinkel M, Walker MD. Role of GPR40 in fatty acid action on the beta cell line INS-1E. Biochem Biophys Res Commun. 2005;335: 97–104. doi: 10.1016/j.bbrc.2005.07.042 16081037
24. Mendez CF, Leibiger IB, Leibiger B, Høy M, Gromada J, Berggren P, et al. Rapid association of protein kinase C-epsilon with insulin granules is essential for insulin exocytosis. J Biol Chem. 2003;278: 44753–44757. doi: 10.1074/jbc.M308664200 12941947
25. Yedovitzky M, Mochly-rosen D, Johnson JA, Gray MO, Ron D, Abramovitch E, et al. Translocation inhibitors define specificity of protein kinase C isoenzymes in pancreatic beta-cells. J Biol Chem. 1997;272: 1417–1420. doi: 10.1074/jbc.272.3.1417 8999804
26. Mogami H, Zhang H, Suzuki Y, Urano T, Saito N, Kojima I, et al. Decoding of short-lived Ca2+ influx signals into long term substrate phosphorylation through activation of two distinct classes of protein kinase C. J Biol Chem. 2003;278: 9896–9904. doi: 10.1074/jbc.M210653200 12514176
27. Shirai Y, Kashiwagi K, Yagi K, Sakai N, Saito N. Distinct effects of fatty acids on translocation of gamma- and epsilon-subspecies of protein kinase C. J Cell Biol. 1998;143: 511–521. doi: 10.1083/jcb.143.2.511 9786959
28. Asfari M, Janjic D, Meda P, Li G, Halban P, Wollheim C. Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines. Endocrinology. 1992;130: 167–178. doi: 10.1210/endo.130.1.1370150 1370150
29. Derossi D, Chassaing G, Prochiantz A. Trojan peptides: the penetratin system for intracellular delivery. Trends Cell Biol. 1998;8: 84–87. 9695814
30. Fischer PM, Zhelev NZ, Wang S, Melville JE, Fåhraeus R LD. Structure-activity relationship of truncated and substituted analogues of the intracellular delivery vector Penetratin. J Pept Res. 2000;55: 163–172. doi: 10.1034/j.1399-3011.2000.00163.x 10784032
31. Harris TE, Persaud SJ, Jones PM. Pseudosubstrate peptide inhibitors of beta-cell protein kinases: altered selectivity after myristoylation. Mol Cell Endocrinol. 1999;155: 61–68. doi: 10.1016/s0303-7207(99)00114-8 10580839
32. Zoukhri D, Hodges RR, Sergheraert C, Toker A, Dartt DA. Lacrimal gland PKC isoforms are differentially involved in agonist-induced protein secretion. Am J Physiol. 1997;272: C263–C269. doi: 10.1152/ajpcell.1997.272.1.C263 9038832
33. Yamada S, Komatsu M, Sato Y, Yamauchi K, Kojima I, Aizawa T, et al. Time-dependent stimulation of insulin exocytosis by 3’,5’-cyclic adenosine monophosphate in the rat islet beta-cell. Endocrinology. 2002;143: 4203–4209. doi: 10.1210/en.2002-220368 12399413
34. Blackshear PJ. The MARCKS family of cellular protein kinase C substrates. J Biol Chem. 1993;268: 1501–1504. 8420923
35. Papers JBC, Doi M, Ohmori S, Sakai N, Shirai Y, Yamamoto H, et al. Importance of protein kinase C targeting for the phosphorylation of its substrate, myristoylated alanine-rich C-kinase substrate. J Biol Chem. 2000;275: 26449–26457. doi: 10.1074/jbc.M003588200 10840037
36. Clapham DE. Calcium signaling. Cell. 1995;80: 259–268. doi: 10.1016/0092-8674(95)90408-5 7834745
37. Barg S. Mechanisms of exocytosis in insulin-secreting B-cells and glucagon-secreting A-cells. Pharmacol Toxicol. 2003;92: 3–13. 12710591
38. Proks P, Lippiat JD. Membrane ion channels and diabetes. Curr Pharm Des. 2006;12: 485–501. doi: 10.2174/138161206775474431 16472141
39. Rendell M. The role of sulphonylureas in the management of type 2 diabetes mellitus. Drugs. 2004;64: 1339–1358. doi: 10.2165/00003495-200464120-00006 15200348
40. Mears D. Regulation of Insulin Secretion in Islets of Langerhans by Ca2+Channels. J Membr Biol. 2004;200: 57–66. doi: 10.1007/s00232-004-0692-9 15520904
41. Hanoune J DN. Regulation and role of adenylyl cyclase isoforms. Annu Rev Pharmacol Toxicol. 2001;41: 145–174. doi: 10.1146/annurev.pharmtox.41.1.145 11264454
42. Wuttke A, Idevall-hagren O, Tengholm A. P2Y1receptor-dependent diacylglycerol signaling microdomains in β cells promote insulin secretion. FASEB J. 2013;27: 1610–1620. doi: 10.1096/fj.12-221499 23299857
43. Wuttke A, Yu Q, Tengholm A. Autocrine Signaling Underlies Fast Repetitive Plasma Membrane Translocation of Conventional and Novel Protein Kinase C Isoforms in β Cells. J Biol Chem. Nature Publishing Group; 2016;291: 14986–14995. doi: 10.1074/jbc.M115.698456 27226533
44. Malaisse WJ, Sener A, Herchuelz A, Poloczek P, Carpinelli AR, Winand J, et al. Insulinotropic Effect of the Tumor Promoter 12-O-Tetradecanoylphorbol-13- Acetate in Rat Pancreatic Islets. Cancer Res. 1980;40: 3827–3832. 6254641
45. Bozem M, NenQuin M, Henquin JC. The Ionic, Electrical, and Secretory Effects of Protein Kinase C Activation in Mouse Pancreatic B-Cells: Studies with a Phorbol Ester. Endocrinology. 1987;121: 1025–1033. doi: 10.1210/endo-121-3-1025 3304975
46. Easom RA, Hughes JH, Landt M, Wolf BA, Turk J, Mcdaniel ML. Comparison of effects of phorbol esters and glucose on protein kinase C activation and insulin secretion in pancreatic islets. Biochem J. 1989;264: 27–33. doi: 10.1042/bj2640027 2690823
47. Sakuma K, Yabuki C, Maruyama M, Abiru A, Komatsu H, Negoro N, et al. Fasiglifam (TAK-875) has dual potentiating mechanisms via Gαq-GPR40/FFAR1 signaling branches on glucose-dependent insulin secretion. Pharmacol Res Perspect. 2016;4: e00237. doi: 10.1002/prp2.237 27433346
48. Yamada H, Yoshida M, Ito K, Dezaki K, Yada T, Ishikawa S, et al. Potentiation of Glucose-stimulated Insulin Secretion by the GPR40 –PLC–TRPC Pathway in Pancreatic β -Cells. Sientific Reports. Nature Publishing Group; 2016;6: 25912. doi: 10.1038/srep25912 27180622
49. Warwar N, Dov A, Abramovitch E, Wu R, Jmoudiak M, Haber E, et al. PKCepsilon mediates glucose-regulated insulin production in pancreatic beta-cells. Biochim Biophys Acta. 2008;1783: 1929–1934. doi: 10.1016/j.bbamcr.2008.04.007 18486624
50. Santo-domingo J, Chareyron I, Dayon L, Galindo AN, Cominetti O, Gimenes MPG, et al. Coordinated activation of mitochondrial respiration and exocytosis mediated by PKC signaling in pancreatic β cells. FASEB J. 2017;31: 1028–1045. doi: 10.1096/fj.201600837R 27927723
51. Fransson U, Rosengren AH, Schuit FC, Renström E, Mulder H. Anaplerosis via pyruvate carboxylase is required for the fuel-induced rise in the ATP:ADP ratio in rat pancreatic islets. Diabetologia. 2006;49: 1578–1586. doi: 10.1007/s00125-006-0263-y 16752176
52. Zhang H, Nagasawa M, Yamada S, Mogami H, Suzuki Y, Kojima I. Bimodal role of conventional protein kinase C in insulin secretion from rat pancreatic beta cells. J Physiol. 2004;561: 133–147. doi: 10.1113/jphysiol.2004.071241 15388777
53. Nolan CJ, Madiraju MSR, Delghingaro-Augusto V, Peyot M-L, Prentki M. Fatty acid signaling in the beta-cell and insulin secretion. Diabetes. 2006;55: S16–S23. doi: 10.2337/db06-s003 17130640
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