Bibliography

1. Solinas G, Vilcu C, Neels JG, et al. JNK1 in hematopoietically derived cells contributes to diet-induced in ammation and insulin resistance without affecting obesity. Cell Metab. 2007;6:386-397.

2. Wang K, Grivennikov SI, Karin M. Implications of anti-cytokine therapy in colorectal cancer and autoimmune diseases. Ann Rheum Dis. 2013;72(suppl 2):ii100-ii103.

3. Changeux JP. The feedback control mechanisms of biosynthetic L-threonine deaminase by L-isoleucine. Cold Spring Harb Symp Quant Biol. 1961;26:313-318.

4. Monod J, Wyman J, Changeux JP. On the nature of allosteric transitions: a plausible model. J Mol Biol. 1965;12:88-118.

5. Iwata S, Kamata K, Yoshida S, Minowa T, Ohta T. T and R states in the crystals of bacterial L-lactate dehydrogenase reveal the mechanism for allosteric control. Nat Struct Biol. 1994;1:176-185.

6. Koshland DE Jr, Némethy G, Filmer D. Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry. 1966;5:365-385.

7. Bu Z, Callaway DJ. Proteins move! Protein dynamics and long-range allostery in cell signaling. Adv Protein Chem Struct Biol. 2011;83:163-221.

8. Changeux JP, Christopoulos A. Allosteric modulation as a unifying mechanism for receptor function and regulation. Cell. 2016;166:1084-1102.

9. Bocquet N, Nury H, Baaden M, et al. X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature. 2009;457:111-114.

10. Bhaskar V, Goldfine ID, Bedinger DH, et al. A fully human, allosteric monoclonal antibody that activates the insulin receptor and improves glycemic control. Diabetes. 2012;61:1263-1271.

11. Issafras H, Bedinger DH, Corbin JA, et al. Selective allosteric antibodies to the insulin receptor for the treatment of hyperglycemic and hypoglycemic disorders. J Diabetes Sci Technol. 2014;8:865-873.

12. Milligan G, Alvarez-Curto E, Hudson BD, Prihandoko R, Tobin AB. FFA4/GPR120: pharmacology and therapeutic opportunities. Trends Pharmacol Sci. 2017;38:809-821.

13. Dunér P, Al-Amily IM, Soni A, et al. Adhesion G protein-coupled receptor G1 (ADGRG1/GPR56) and pancreatic -cell function. J Clin Endocrinol Metab. 2016;101:4637-4645.

14. Husted AS, Trauelsen M, Rudenko O, Hjorth SA, Schwartz TW. GPCR-mediated signaling of metabolites. Cell Metab. 2017;25:777-796.

15. Krug AW, Vaddady P, Railkar RA, et al. Leveraging a clinical phase Ib proof-of-concept study for the GPR40 agonist MK-8666 in patients with type 2 diabetes for model-informed phase II dose selection. Clin Transl Sci. 2017;10:404-411.

16. Srivastava A, Yano J, Hirozane Y, et al. High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875. Nature. 2014;513:124-127.

17. Kaku K, Araki T, Yoshinaka R. Randomized, double-blind, dose-ranging study of TAK-875, a novel GPR40 agonist, in Japanese patients with inadequately controlled type 2 diabetes. Diabetes Care. 2013;36:245-250.

18. Guo L, Parker DL, Zang Y, et al. Discovery and optimization of a novel triazole series of GPR142 agonists for the treatment of type 2 diabetes. ACS Med Chem Lett. 2016;7:1107-1111.

19. Wilson JE, Kurukulasuriya R, Sinz C, et al. Discovery and development of benzo-[1,2,4]-triazolo-[1,4]-oxazepine GPR142 agonists for the treatment of diabetes. Bioorg Med Chem Lett. 2016;26:2947-2951.

20. Kowluru A, Kowluru RA. Protein prenylation in islet -cell function in health and diabetes: putting the pieces of the puzzle together. Biochem Pharmacol. 2015;98:363-370.

21. Sidarala V, Kowluru A. Exposure to chronic hyperglycemic conditions results in Ras-related C3 botulinum toxin substrate 1 (Rac1)-mediated activation of p53 and ATM kinase in pancreatic -cells. Apoptosis. 2017;22:597-607.

22. Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS. Mammalian sweet taste receptors. Cell. 2001;106:381-390.

23. Kojima I, Nakagawa Y, Ohtsu Y, Medina A, Nagasawa M. Sweet taste-sensing receptors expressed in pancreatic β-cells: sweet molecules act as biased agonists. Endocrinol Metab (Seoul). 2014;29:12-19.

24. Nakagawa Y, Nagasawa M, Mogami H, Lohse M, Ninomiya Y, Kojima I. Multimodal function of the sweet taste receptor expressed in pancreatic β-cells: generation of diverse patterns of intracellular signals by sweet agonists. Endocr J. 2013;601:191-1206.

25. Medina J, Nakagawa Y, Nagasawa M, et al. Positive allosteric modulation of the calcium-sensing receptor by physiological concentrations of glucose. J Biol Chem. 2016;291:23126-23135.

26. Nakagawa Y, Ohtsu Y, Nagasawa M, Shibata H, Kojima I. Glucose promotes its own metabolism by acting on the cell surface glucose-sensing receptor T1R3. Endocr J. 2014;61:119-131.

27. Kojima I, Nakagawa Y, Hamano K, Medina J, Li L, Nagasawa M. Glucose-sensing receptor T1R3: a new signaling receptor activated by glucose in pancreatic β-cells. Biol Pharm Bull. 2015;38:674-679.

28. Kojima I, Nakagawa Y, Ohtsu Y, Hamano K, Medina J, Nagasawa M. Return of the glucoreceptor: glucose activates the glucose-sensing receptor T1R3 and facilitates metabolism in pancreatic β-cells. J Diabetes Investig. 2015;6:256-263.

29. Welters A, Lammert E, Mayatepek E, Meissner T. Need for better diabetes treatment: the therapeutic potential of NMDA receptor antagonists. Klin Padiatr. 2017;229:14-20.

30. Werling LL, Lauterbach EC, Calef U. Dextromethorphan as a potential neuroprotective agent with unique mechanisms of action. Neurologist. 2007;13:272-293.

31. Wu TC, Chao CY, Lin SJ, Chen JW. Low-dose dextromethorphan, a NADPH oxidase inhibitor, reduces blood pressure and enhances vascular protection in experimental hypertension. PLoS One. 2012;7:e46067.

32. Rutter GA, Hodson DJ, Chabosseau P, Haythorne E, Pullen TJ, Leclerc I. Local and regional control of calcium dynamics in the pancreatic islet. Diabetes Obes Metab. 2017;19(suppl 1):30-41.

33. Marmugi A, Parnis J, Chen X, et al. Sorcin links pancreatic β-cell lipotoxicity to ER Ca2+ stores. Diabetes. 2016;65:1009-1021.

34. Mitchell RK, Nguyen-Tu MS, Chabosseau P, et al.  e transcription factor Pax6 is required for pancreatic β cell identity, glucose-regulated ATP synthesis, and Ca2+ dynamics in adult mice. J Biol Chem. 2017;292:8892-8906.

35. Tengholm A, Gylfe E. cAMP signalling in insulin and glucagon secretion. Diabetes Obes Metab. 2017;19(suppl 1):42-53.

36. Tian G, Sol ER, Xu Y, Shuai H, Tengholm A. Tengholm, Impaired cAMP generation contributes to defective glucosestimulated insulin secretion a er long-term exposure to palmitate. Diabetes. 2015;64:904-915.

37. Rosengren AH, Jokubka R, Tojjar D, et al. Overexpression of alpha2A-adrenergic receptors contributes to type 2 diabetes. Science. 2010;327:217-220.

38. Hodson DJ, Mitchell RK, Marselli L, et al. ADCY5 couples glucose to insulin secretion in human islets. Diabetes. 2014;63:3009-3021.

39. Seino S, Sugawara K, Yokoi N, Takahashi H. β-Cell signalling and insulin secretagogues: a path for improved diabetes therapy. Diabetes Obes Metab. 2017;19(suppl 1):22-29.

40. Takahashi H, Shibasaki T, Park JH, et al. Role of Epac2A/Rap1 signaling in interplay between incretin and sulfonylurea in insulin secretion. Diabetes. 2015;64:1262-1272.

41. Yabe D, Eto T, Shiramoto M, et al. Effects of DPP-4 inhibitor linagliptin and GLP-1 receptor agonist liraglutide on physiological response to hypoglycaemia in Japanese subjects with type 2 diabetes: a randomized, open-label, 2-arm parallel comparative, exploratory trial. Diabetes Obes Metab. 2017;19(suppl 1):442-447.

42. Newgard CB. Metabolomics and metabolic diseases: where do we stand? Cell Metab. 2017;25:43-56.

43. Gooding JR, Jensen MV, Newgard CB. Metabolomics applied to the pancreatic islet. Arch Biochem Biophys. 2016;589:120-130.

44. Ferdaoussi M, Dai X, Jensen MV, et al. Isocitrate-to-SENP1 signaling amplifies insulin secretion and rescues dysfunctional β cells. J Clin Invest. 2015;125:3847-3860.

45. Jensen MV, Haldeman JM, Zhang H, et al. Control of voltage-gated potassium channel Kv2.2 expression by pyruvateisocitrate cycling regulates glucose-stimulated insulin secretion. J Biol Chem. 2013;288:23128-23140.

46. Prentki M, Madiraju SR. Glycerolipid metabolism and signaling in health and disease. Endocr Rev. 2008;29:647-676.

47. Prentki M, Matschinsky FM, Madiraju SR. Metabolic signaling in fuel-induced insulin secretion. Cell Metab. 2013;18:162-185.

48. Attané C, Peyot ML, Lussier R, et al. A beta cell ATGL-lipolysis/adipose tissue axis controls energy homeostasis and body weight via insulin secretion in mice. Diabetologia. 2016;59:2654-2663.

49. Zhao S, Mugabo Y, Iglesias J, et al. α/β-Hydrolase domain-6-accessible monoacylglycerol controls glucose-stimulated insulin secretion. Cell Metab. 2014;19:993-1007.

50. Müller A, Neukam M, Ivanova A, et al. A global approach for quantitative super resolution and electron microscopy on cryo and epoxy sections using self-labeling protein tags. Sci Rep. 2017;7:23.

51. Ivanova A, Kalaidzidis Y, Dirkx R, et al. Age-dependent labeling and imaging of insulin secretory granules. Diabetes. 2013;62:3687-3696.

52. Hoboth P, Müller A, Ivanova A, et al. Aged insulin granules display reduced microtubule-dependent mobility and are disposed within actin-positive multigranular bodies. Proc Natl Acad Sci U S A. 2015;112:E667-E676.

53. Pejler G, Hu Frisk JM, Sjöström D, Paivandy A, Öhrvik H. Acidic pH is essential for maintaining mast cell secretory granule homeostasis. Cell Death Dis. 2017;8:e2785.

54. Zhu D, Xie L, Karimian N, et al. Munc18c mediates exocytosis of pre-docked and newcomer insulin granules underlying biphasic glucose stimulated insulin secretion in human pancreatic beta-cells. Mol Metab. 2015;4:418-426.

55. Xie L, Zhu D, Dolai S, et al. Syntaxin-4 mediates exocytosis of pre-docked and newcomer insulin granules underlying biphasic glucose-stimulated insulin secretion in human pancreatic beta cells. Diabetologia. 2015;58:1250-1259.

56. Wheeler SE, Stacey HM, Nahaei Y, et al.  e SNARE protein syntaxin1a plays an essential role in biphasic exocytosis of the incretin hormone glucagon-like peptide-1. Diabetes. 2017;66:2327-2338.

57. Lam PP, Leung YM, Sheu L, et al. Transgenic mouse overexpressing syntaxin-1A as a diabetes model. Diabetes. 2005;54:2744-2754.

58. Zhu D, Xie L, Kang Y, et al. Syntaxin 2 acts as inhibitory SNARE for insulin granule exocytosis. Diabetes. 2017;66:948-959.

59. Rorsman P, Braun M. Regulation of insulin secretion in human pancreatic islets. Annu Rev Physiol. 2013;75:155-179.

60. Johnston NR, Mitchell RK, Haythorne E, et al. Beta cell hubs dictate pancreatic islet responses to glucose. Cell Metab. 2016;24:389-401.

61. Xin Y, Kim J, Okamoto H, et al. RNA sequencing of single human islet cells reveals type 2 diabetes genes. Cell Metab. 2016;24:608-615.

62. Xin Y, Kim J, Ni M, et al. Use of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells. Proc Natl Acad Sci U S A. 2016;113:3293-3298.

63. Nikolova G, Jabs N, Konstantinova I, et al. The vascular basement membrane: a niche for insulin gene expression and beta cell proliferation. Dev Cell. 2006;10:397-405.

64. Ahren B. Autonomic regulation of islet hormone secretion–implications for health and disease. Diabetologia. 2000;43:393-410.

65. Esni F, Täljedal IB, Perl AK, Cremer H, Christofori G, Semb H. Neural cell adhesion molecule (N-CAM) is required for cell type segregation and normal ultrastructure in pancreatic islets. J Cell Biol. 1999;144:325-337.

66. Brissova M, Aamodt K, Brahmachary P, et al. Islet microenvironment, modulated by vascular endothelial growth factor-A signaling, promotes β cell regeneration. Cell Metab. 2014;19:498-511.

67. Longuet C, Robledo AM, Dean ED, et al. Liver-specific disruption of the murine glucagon receptor produces α-cell hyperplasia: evidence for a circulating α-cell growth factor. Diabetes. 2013;62:1196-1205.

68. Dean ED, Li M, Prasad N, et al. Interrupted glucagon signaling reveals hepatic α cell axis and role for L-glutamine in α cell proliferation. Cell Metab. 2017;25:1362-1373.e5.

69. Ben-Zvi D, Barrandon O, Hadley S, Blum B, Peterson QP, Melton DA. Angptl4 links α-cell proliferation following glucagon receptor inhibition with adipose tissue triglyceride metabolism. Proc Natl Acad Sci U S A. 2015;112:15498-15503.

70. Guay C, Regazzi R. New emerging tasks for microRNAs in the control of β-cell activities. Biochim Biophys Acta. 2016;1861:2121-2129.

71. Guay C, Menoud V, Rome S, Regazzi R. Horizontal transfer of exosomal microRNAs transduce apoptotic signals between pancreatic beta-cells. Cell Commun Signal. 2015;13:17.

72. Grieco FA, Sebastiani G, Juan-Mateu J, et al. MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p regulate the expression of proapoptotic BH3-only proteins DP5 and PUMA in human pancreatic β-cells. Diabetes. 2017;66:100-112.

73. Guay C, Regazzi R. Exosomes as new players in metabolic organ cross-talk. Diabetes Obes Metab. 2017;19(suppl 1):137-146.