Molecular mechanisms redirecting the GLP-1 receptor signalling profile in pancreatic β-cells during type 2 diabetes

References

1. Del Prato S, Tiengo A. The importance of first-phase insulin secretion: implications for the therapy of type 2 diabetes mellitus. Diabetes Metab Res Rev 2001;17:164–74.10.1002/dmrr.198Search in Google Scholar PubMed

2. Goldfine AB, Bouche C, Parker RA, Kim C, Kerivan A, Soeldner JS, Martin BC, Warram JH, Kahn CR. Insulin resistance is a poor predictor of type 2 diabetes in individuals with no family history of disease. Proc Natl Acad Sci USA 2003;100:2724–9.10.1073/pnas.0438009100Search in Google Scholar PubMed PubMed Central

3. Henquin JC. Regulation of insulin secretion: a matter of phase control and amplitude modulation. Diabetologia 2009;52:739–51.10.1007/s00125-009-1314-ySearch in Google Scholar PubMed

4. Matschinsky FM. Banting Lecture 1995. A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabetes 1996;45:223–41.10.2337/diabetes.45.2.223Search in Google Scholar

5. Ashcroft FM, Rorsman P. Molecular defects in insulin secretion in type-2 diabetes. Rev Endocr Metab Disord 2004;5:135–42.10.1023/B:REMD.0000021435.87776.a7Search in Google Scholar

6. Prentki M, Nolan, CJ. Islet beta cell failure in type 2 diabetes. J Clin Invest 2006;116:1802–12.10.1172/JCI29103Search in Google Scholar PubMed PubMed Central

7. Brunzell JD, Robertson RP, Lerner RL, Hazzard WR, Ensinck JW, Bierman EL, Porte D Jr. Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests. J Clin Endocrinol Metab 1976;42:222–9.10.1210/jcem-42-2-222Search in Google Scholar PubMed

8. Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC. Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab 2008;10(Suppl 4):32–42.10.1111/j.1463-1326.2008.00969.xSearch in Google Scholar PubMed

9. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003;52:102–10.10.2337/diabetes.52.1.102Search in Google Scholar PubMed

10. Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab 2013;17:819–37.10.1016/j.cmet.2013.04.008Search in Google Scholar PubMed

11. Drucker DJ. Incretin action in the pancreas: potential promise, possible perils, and pathological pitfalls. Diabetes 2013;62:3316–23.10.2337/db13-0822Search in Google Scholar PubMed PubMed Central

12. Doyle ME, Egan JM. Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther 2007;113:546–93.10.1016/j.pharmthera.2006.11.007Search in Google Scholar PubMed PubMed Central

13. Hjollund KR, Deacon CF, Holst JJ. Dipeptidyl peptidase-4 inhibition increases portal concentrations of intact glucagon-like peptide-1 (GLP-1) to a greater extent than peripheral concentrations in anaesthetised pigs. Diabetologia 2011;54:2206–8.10.1007/s00125-011-2168-7Search in Google Scholar PubMed

14. Gilon P, Ravier MA, Jonas JC, Henquin JC. Control mechanisms of the oscillations of insulin secretion in vitro and in vivo. Diabetes 2002;51(Suppl 1):S144–51.10.2337/diabetes.51.2007.S144Search in Google Scholar PubMed

15. Henquin JC, Ravier MA, Nenquin M, Jonas JC, Gilon P. Hierarchy of the beta-cell signals controlling insulin secretion. Eur J Clin Invest 2003;33:742–50.10.1046/j.1365-2362.2003.01207.xSearch in Google Scholar PubMed

16. Benes C, Roisin MP, Van Tan H, Creuzet C, Miyazaki J, Fagard R. Rapid activation and nuclear translocation of mitogen-activated protein kinases in response to physiological concentration of glucose in the MIN6 pancreatic beta cell line. J Biol Chem 1998;273:15507–13.10.1074/jbc.273.25.15507Search in Google Scholar PubMed

17. Costes S, Broca C, Bertrand G, Lajoix AD, Bataille D, Bockaert J, Dalle S. ERK1/2 control phosphorylation and protein level of cAMP-responsive element-binding protein: a key role in glucose-mediated pancreatic beta-cell survival. Diabetes 2006;55:2220–30.10.2337/db05-1618Search in Google Scholar PubMed

18. Longuet C, Broca C, Costes S, Hani EH, Bataille D, Dalle S. Extracellularly regulated kinases 1/2 (p44/42 mitogen-activated protein kinases) phosphorylate synapsin I and regulate insulin secretion in the MIN6 beta-cell line and islets of Langerhans. Endocrinology 2005;146:643–54.10.1210/en.2004-0841Search in Google Scholar PubMed

19. Briaud I, Lingohr MK, Dickson LM, Wrede CE, Rhodes CJ. Differential activation mechanisms of Erk-1/2 and p70(S6K) by glucose in pancreatic beta-cells. Diabetes 2003;52:974–83.10.2337/diabetes.52.4.974Search in Google Scholar PubMed

20. Buteau J, Foisy S, Joly E, Prentki M. Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via transactivation of the epidermal growth factor receptor. Diabetes 2003;52:124–32.10.2337/diabetes.52.1.124Search in Google Scholar PubMed

21. Buteau J, Roduit R, Susini S, Prentki M. Glucagon-like peptide-1 promotes DNA synthesis, activates phosphatidylinositol 3-kinase and increases transcription factor pancreatic and duodenal homeobox gene 1 (PDX-1) DNA binding activity in beta (INS-1)-cells. Diabetologia 1999;42:856–64.10.1007/s001250051238Search in Google Scholar PubMed

22. Buteau J, Foisy S, Rhodes CJ, Carpenter L, Biden TJ, Prentki M. Protein kinase Czeta activation mediates glucagon-like peptide-1-induced pancreatic beta-cell proliferation. Diabetes 2001;50:2237–43.10.2337/diabetes.50.10.2237Search in Google Scholar PubMed

23. Huypens P, Ling Z, Pipeleers D, Schuit F. Glucagon receptors on human islet cells contribute to glucose competence of insulin release. Diabetologia 2000;43:1012–9.10.1007/s001250051484Search in Google Scholar PubMed

24. Arnette D, Gibson TB, Lawrence MC, January B, Khoo S, McGlynn K, Vanderbilt CA, Cobb MH. Regulation of ERK1 and ERK2 by glucose and peptide hormones in pancreatic beta cells. J Biol Chem 2003;278:32517–25.10.1074/jbc.M301174200Search in Google Scholar PubMed

25. Khoo S, Griffen SC, Xia Y, Baer RJ, German MS, Cobb MH. Regulation of insulin gene transcription by ERK1 and ERK2 in pancreatic beta cells. J Biol Chem 2003;278:32969–77.10.1074/jbc.M301198200Search in Google Scholar PubMed

26. Tomimoto S, Hashimoto H, Shintani N, Yamamoto K, Kawabata Y, Hamagami K, Yamagata K, Miyagawa J, Baba A. Overexpression of pituitary adenylate cyclase-activating polypeptide in islets inhibits hyperinsulinemia and islet hyperplasia in agouti yellow mice. J Pharmacol Exp Ther 2004;309:796–803.10.1124/jpet.103.062919Search in Google Scholar PubMed

27. Beguin P, Nagashima K, Nishimura M, Gonoi T, Seino S. PKA-mediated phosphorylation of the human K(ATP) channel: separate roles of Kir6.2 and SUR1 subunit phosphorylation. EMBO J 1999;18:4722–32.10.1093/emboj/18.17.4722Search in Google Scholar PubMed PubMed Central

28. Kang G, Joseph JW, Chepurny OG, Monaco M, Wheeler MB, Bos JL, Schwede F, Genieser HG, Holz GG. Epac-selective cAMP analog 8-pCPT-2′-O-Me-cAMP as a stimulus for Ca2+-induced Ca2+ release and exocytosis in pancreatic beta-cells. J Biol Chem 2003;278:8279–85.10.1074/jbc.M211682200Search in Google Scholar PubMed PubMed Central

29. Seino S, Shibasaki T. PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev 2005;85:1303–42.10.1152/physrev.00001.2005Search in Google Scholar PubMed

30. Shibasaki T, Takahashi H, Miki T, Sunaga Y, Matsumura K, Yamanaka M, Zhang C, Tamamoto A, Satoh T, Miyazaki J, Seino S. Essential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP. Proc Natl Acad Sci USA 2007;104:19333–8.10.1073/pnas.0707054104Search in Google Scholar PubMed PubMed Central

31. Tsuboi T, da Silva Xavier G, Holz GG, Jouaville LS, Thomas AP, Rutter GA. Glucagon-like peptide-1 mobilizes intracellular Ca2+ and stimulates mitochondrial ATP synthesis in pancreatic MIN6 beta-cells. Biochem J 2003;369:287–99.10.1042/bj20021288Search in Google Scholar PubMed PubMed Central

32. Straub SG, Sharp GW. Glucose-dependent insulinotropic polypeptide stimulates insulin secretion via increased cyclic AMP and [Ca2+]1 and a wortmannin-sensitive signalling pathway. Biochem Biophys Res Commun 1996;224:369–74.10.1006/bbrc.1996.1035Search in Google Scholar PubMed

33. Thorens B. Expression cloning of the pancreatic beta cell receptor for the gluco-incretin hormone glucagon-like peptide 1. Proc Natl Acad Sci USA 1992;89:8641–5.10.1073/pnas.89.18.8641Search in Google Scholar PubMed PubMed Central

34. Mayo KE, Miller LJ, Bataille D, Dalle S, Goke B, Thorens B, Drucker DJ. International Union of Pharmacology. XXXV. The glucagon receptor family. Pharmacol Rev 2003;55:167–94.10.1124/pr.55.1.6Search in Google Scholar PubMed

35. Holz GG. Epac: a new cAMP-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cell. Diabetes 2004;53:5–13.10.2337/diabetes.53.1.5Search in Google Scholar PubMed PubMed Central

36. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007;87:1409–39.10.1152/physrev.00034.2006Search in Google Scholar PubMed

37. Seino S, Takahashi H, Fujimoto W, Shibasaki T. Roles of cAMP signalling in insulin granule exocytosis. Diabetes Obes Metab 2009;11(Suppl 4):180–8.10.1111/j.1463-1326.2009.01108.xSearch in Google Scholar PubMed

38. Light PE, Manning Fox JE, Riedel MJ, Wheeler MB. Glucagon-like peptide-1 inhibits pancreatic ATP-sensitive potassium channels via a protein kinase A- and ADP-dependent mechanism. Mol Endocrinol 2002;16:2135–44.10.1210/me.2002-0084Search in Google Scholar PubMed

39. Leiser M, Fleischer N. cAMP-dependent phosphorylation of the cardiac-type alpha 1 subunit of the voltage-dependent Ca2+ channel in a murine pancreatic beta-cell line. Diabetes 1996;45:1412–8.10.2337/diabetes.45.10.1412Search in Google Scholar

40. Lester LB, Langeberg LK, Scott JD. Anchoring of protein kinase A facilitates hormone-mediated insulin secretion. Proc Natl Acad Sci USA 1997;94:14942–7.10.1073/pnas.94.26.14942Search in Google Scholar PubMed PubMed Central

41. Holz GG, Kuhtreiber WM, Habener JF. Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1(7–37). Nature 1993;361:362–5.10.1038/361362a0Search in Google Scholar

42. Ding SY, Nkobena A, Kraft CA, Markwardt ML, Rizzo MA. Glucagon-like peptide 1 stimulates post-translational activation of glucokinase in pancreatic beta cells. J Biol Chem 2011;286:16768–74.10.1074/jbc.M110.192799Search in Google Scholar

43. Thorens B. Molecular and cellular physiology of GLUT-2, a high-Km facilitated diffusion glucose transporter. Int Rev Cytol 1992;137:209–38.10.1016/S0074-7696(08)62677-7Search in Google Scholar

44. Loder MK, da Silva Xavier G, McDonald A, Rutter GA. TCF7L2 controls insulin gene expression and insulin secretion in mature pancreatic beta-cells. Biochem Soc Trans 2008;36:357–9.10.1042/BST0360357Search in Google Scholar PubMed

45. Liu Z, Habener JF. Glucagon-like peptide-1 activation of TCF7L2-dependent Wnt signaling enhances pancreatic beta cell proliferation. J Biol Chem 2008;283:8723–35.10.1074/jbc.M706105200Search in Google Scholar PubMed PubMed Central

46. Jhala US, Canettieri G, Screaton RA, Kulkarni RN, Krajewski S, Reed J. Walker J, Lin X, White M, Montminy M. cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2. Genes Dev 2003;17:1575–80.10.1101/gad.1097103Search in Google Scholar PubMed PubMed Central

47. Dalle S, Quoyer J, Varin E, Costes S. Roles and regulation of the transcription factor CREB in pancreatic beta -cells. Curr Mol Pharmacol 2011;4:187–95.10.2174/1874467211104030187Search in Google Scholar PubMed

48. Costes S, Vandewalle B, Tourrel-Cuzin C, Broca C, Linck N, Bertrand G, Kerr-Conte J, Portha B, Pattou F, Bockaert J, Dalle S. Degradation of cAMP-responsive element-binding protein by the ubiquitin-proteasome pathway contributes to glucotoxicity in beta-cells and human pancreatic islets. Diabetes 2009;58:1105–15.10.2337/db08-0926Search in Google Scholar PubMed PubMed Central

49. Quoyer J, Longuet C, Broca C, Linck N, Costes S, Varin E, Bockaert J, Bertrand G, Dalle S. GLP-1 mediates antiapoptotic effect by phosphorylating Bad through a beta-arrestin 1-mediated ERK1/2 activation in pancreatic beta-cells. J Biol Chem 2010;285:1989–2002.10.1074/jbc.M109.067207Search in Google Scholar PubMed PubMed Central

50. Gomez E, Pritchard C, Herbert TP. cAMP-dependent protein kinase and Ca2+ influx through L-type voltage-gated calcium channels mediate Raf-independent activation of extracellular regulated kinase in response to glucagon-like peptide-1 in pancreatic beta-cells. J Biol Chem 2002;277:48146–51.10.1074/jbc.M209165200Search in Google Scholar PubMed

51. Kim MJ, Kang JH, Park YG, Ryu GR, Ko SH, Jeong IK, Koh KH, Rhie DJ, Yoon SH, Hahn SJ, Kim MS, Jo YH. Exendin-4 induction of cyclin D1 expression in INS-1 beta-cells: involvement of cAMP-responsive element. J Endocrinol 2006;188:623–33.10.1677/joe.1.06480Search in Google Scholar PubMed

52. Cornu, M, Yang JY, Jaccard E, Poussin C, Widmann C, Thorens B. Glucagon-like peptide-1 protects beta-cells against apoptosis by increasing the activity of an IGF-2/IGF-1 receptor autocrine loop. Diabetes 2009;58:1816–25.10.2337/db09-0063Search in Google Scholar PubMed PubMed Central

53. Cornu M, Modi H, Kawamori D, Kulkarni RN, Joffraud M, Thorens B. Glucagon-like peptide-1 increases beta-cell glucose competence and proliferation by translational induction of insulin-like growth factor-1 receptor expression. J Biol Chem 2010;285:10538–45.10.1074/jbc.M109.091116Search in Google Scholar PubMed PubMed Central

54. Luttrell LM, Roudabush FL, Choy EW, Miller WE, Field ME, Pierce KL, Lefkowitz RJ. Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds. Proc Natl Acad Sci USA 2001;98:2449–54.10.1073/pnas.041604898Search in Google Scholar PubMed PubMed Central

55. Kendall RT, Luttrell LM. Diversity in arrestin function. Cell Mol Life Sci 2009;66:2953–73.10.1007/s00018-009-0088-1Search in Google Scholar PubMed

56. DeWire SM, Ahn S, Lefkowitz RJ, Shenoy SK. Beta-arrestins and cell signaling. Annu Rev Physiol 2007;69:483–510.10.1146/annurev.physiol.69.022405.154749Search in Google Scholar PubMed

57. Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 1986;29:46–52.10.1007/BF02427280Search in Google Scholar PubMed

58. Meier JJ, Nauc, MA. Is the diminished incretin effect in type 2 diabetes just an epi-phenomenon of impaired beta-cell function? Diabetes 2010;59:1117–25.10.2337/db09-1899Search in Google Scholar PubMed PubMed Central

59. Knop FK, Vilsboll T, Hojberg PV, Larsen S, Madsbad S, Volund A, Holst JJ, Krarup T. Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? Diabetes 2007;56:1951–9.10.2337/db07-0100Search in Google Scholar PubMed

60. Fritsche A, Stefan N, Hardt E, Haring H, Stumvoll M. Characterisation of beta-cell dysfunction of impaired glucose tolerance: evidence for impairment of incretin-induced insulin secretion. Diabetologia 2000;43:852–8.10.1007/s001250051461Search in Google Scholar PubMed

61. Ahren B. Incretin dysfunction in type 2 diabetes: clinical impact and future perspectives. Diabetes Metab 2013;39:195–201.10.1016/j.diabet.2013.03.001Search in Google Scholar PubMed

62. Herzberg-Schafer S, Heni M, Stefan N, Haring HU, Fritsche A. Impairment of GLP1-induced insulin secretion: role of genetic background, insulin resistance and hyperglycaemia. Diabetes Obes Metab 2012;14(Suppl 3):85–90.10.1111/j.1463-1326.2012.01648.xSearch in Google Scholar PubMed

63. Schafer SA, Mussig K, Staiger H, Machicao F, Stefan N, Gallwitz B, Haring HU, Fritsche A. A common genetic variant in WFS1 determines impaired glucagon-like peptide-1-induced insulin secretion. Diabetologia 2009;52:1075–82.10.1007/s00125-009-1344-5Search in Google Scholar PubMed

64. Simonis-Bik AM, Eekhoff EM, de Moor MH, Kramer MH, Boomsma DI, Heine RJ, Dekker JM, Maassen JA, t Hart LM, Diamant M, de Geus EJ. Genetic influences on the insulin response of the beta cell to different secretagogues. Diabetologia 2009;52:2570–7.10.1007/s00125-009-1532-3Search in Google Scholar PubMed

65. Schafer SA, Tschritter O, Machicao F, Thamer C, Stefan N, Gallwitz B, Holst JJ, Dekker JM, t Hart LM, Nijpels G, van Haeften TW, Haring HU, Fritsche A. Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Diabetologia 2007;50:2443–50.10.1007/s00125-007-0753-6Search in Google Scholar PubMed PubMed Central

66. Shu L, Matveyenko AV, Kerr-Conte J, Cho JH, McIntosh CH, Maedler K. Decreased TCF7L2 protein levels in type 2 diabetes mellitus correlate with downregulation of GIP- and GLP-1 receptors and impaired beta-cell function. Hum Mol Genet 2009;18:2388–99.10.1093/hmg/ddp178Search in Google Scholar PubMed PubMed Central

67. Mussig K, Staiger H, Machicao F, Haring HU, Fritsche, A. Genetic variants affecting incretin sensitivity and incretin secretion. Diabetologia 2010;53:2289–97.10.1007/s00125-010-1876-8Search in Google Scholar PubMed

68. Hojberg PV, Zander M, Vilsboll T, Knop FK, Krarup T, Volund A, Holst JJ, Madsbad S. Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes. Diabetologia 2008;51:632–40.10.1007/s00125-008-0943-xSearch in Google Scholar PubMed

69. Hojberg PV, Vilsboll T, Rabol R, Knop FK, Bache M, Krarup T, Holst JJ, Madsbad S. Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia 2009;52:199–207.10.1007/s00125-008-1195-5Search in Google Scholar PubMed

70. Xu G, Kaneto H, Laybutt DR, Duvivier-Kali VF, Trivedi N, Suzuma K, King GL, Weir, GC, Bonner-Weir S. Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes. Diabetes 2007;56:1551–8.10.2337/db06-1033Search in Google Scholar PubMed

71. Rajan S, Dickson LM, Mathew E, Orr CM, Ellenbroek JH, Philipson LH, Wicksteed B. Chronic hyperglycemia downregulates GLP-1 receptor signaling in pancreatic beta-cells via protein kinase A. Mol Metab 2015;4:265–76.10.1016/j.molmet.2015.01.010Search in Google Scholar PubMed PubMed Central

72. Kang ZF, Deng Y, Zhou Y, Fan RR, Chan JC, Laybutt DR, Luzuriaga J, Xu G. Pharmacological reduction of NEFA restores the efficacy of incretin-based therapies through GLP-1 receptor signalling in the beta cell in mouse models of diabetes. Diabetologia 2013;56:423–33.10.1007/s00125-012-2776-xSearch in Google Scholar PubMed PubMed Central

73. Kimple ME, Keller MP, Rabaglia MR, Pasker RL, Neuman JC, Truchan NA, Brar HK, Attie AD. Prostaglandin E2 receptor, EP3, is induced in diabetic islets and negatively regulates glucose- and hormone-stimulated insulin secretion. Diabetes 2013;62:1904–12.10.2337/db12-0769Search in Google Scholar PubMed PubMed Central

74. McMahon M, Gerich J, Rizza R. Effects of glucocorticoids on carbohydrate metabolism. Diabetes Metab Rev 1988;4:17–30.10.1002/dmr.5610040105Search in Google Scholar PubMed

75. Rafacho A, Ortsater H, Nadal A, Quesada I. Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes. J Endocrinol 2014;223:R49–62.10.1530/JOE-14-0373Search in Google Scholar PubMed

76. Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov 2006;5:993–6.10.1038/nrd2199Search in Google Scholar PubMed

77. van Raalte DH, Ouwens DM, Diamant M. Novel insights into glucocorticoid-mediated diabetogenic effects: towards expansion of therapeutic options? Eur J Clin Invest 2009;39:81–93.10.1111/j.1365-2362.2008.02067.xSearch in Google Scholar PubMed

78. Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis. J Clin Endocrinol Metab 2009;94:2692–701.10.1210/jc.2009-0370Search in Google Scholar PubMed

79. Origuchi T, Yamaguchi S, Inoue A, Kazaura Y, Matsuo N, Abiru N, Kawakami A, Eguchi K. Increased incidence of pre-diabetes mellitus at a department of rheumatology: a retrospective study. Mod Rheumatol 2011;21:495–9.10.3109/s10165-011-0433-8Search in Google Scholar

80. Di Dalmazi G, Pagotto U, Pasquali R, Vicennati V. Glucocorticoids and type 2 diabetes: from physiology to pathology. J Nutr Metab 2012:2012;525093.10.1155/2012/525093Search in Google Scholar PubMed PubMed Central

81. Lambillotte C, Gilon P, Henquin JC. Direct glucocorticoid inhibition of insulin secretion. An in vitro study of dexamethasone effects in mouse islets. J Clin Invest 1997;99:414–23.10.1172/JCI119175Search in Google Scholar

82. Gremlich S, Roduit R, Thorens B. Dexamethasone induces posttranslational degradation of GLUT2 and inhibition of insulin secretion in isolated pancreatic beta cells. Comparison with the effects of fatty acids. J Biol Chem 1997;272:3216–22.10.1074/jbc.272.6.3216Search in Google Scholar

83. Ullrich S, Berchtold S, Ranta F, Seebohm G, Henke G, Lupescu A, Mack AF, Chao CM, Su J, Nitschke R, Alexander D, Friedrich B, Wulff P, Kuhl D, Lang F. Serum- and glucocorticoid-inducible kinase 1 (SGK1) mediates glucocorticoid-induced inhibition of insulin secretion. Diabetes 2005;54:1090–9.10.2337/diabetes.54.4.1090Search in Google Scholar

84. Eriksen M, Jensen DH, Tribler S, Holst JJ, Madsbad S, Krarup T. Reduction of insulinotropic properties of GLP-1 and GIP after glucocorticoid-induced insulin resistance. Diabetologia 2015;58:920–8.10.1007/s00125-015-3522-ySearch in Google Scholar

85. Ritzel RA, Kleine N, Holst JJ, Willms B, Schmiegel W, Nauck MA. Preserved GLP-1 effects in a diabetic patient with Cushing’s disease. Exp Clin Endocrinol Diabetes 2007;115:146–50.10.1055/s-2007-955096Search in Google Scholar

86. Matsuo K, Nambu T, Matsuda Y, Kanai Y, Yonemitsu S, Muro S, Oki S. Evaluation of the effects of exenatide administration in patients with type 2 diabetes with worsened glycemic control caused by glucocorticoid therapy. Intern Med 2013;52:89–95.10.2169/internalmedicine.52.8622Search in Google Scholar

87. Bamberger CM, Schulte HM, Chrousos GP. Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev 1996;17:245–61.10.1210/edrv-17-3-245Search in Google Scholar

88. DeRijk RH, Schaaf M, de Kloet ER. Glucocorticoid receptor variants: clinical implications. J Steroid Biochem Mol Biol 2002;81:103–22.10.1016/S0960-0760(02)00062-6Search in Google Scholar

89. Baggio LL, Kim JG, Drucker DJ. Chronic exposure to GLP-1R agonists promotes homologous GLP-1 receptor desensitization in vitro but does not attenuate GLP-1R-dependent glucose homeostasis in vivo. Diabetes 2004;53(Suppl 3):S205–14.10.2337/diabetes.53.suppl_3.S205Search in Google Scholar PubMed