Lipotoxicity disrupts incretin-regulated human β cell connectivity

Journal of Clinical Investigation

Volumn 123, Issue 10, 2013, Pages 4182-4194

  Hodson, David J ^a   Mitchell, Ryan K ^a   Bellomo, Elisa A ^a   Sun, Gao ^a   Vinet, Laurent ^b   Meda, Paolo ^b   Li, Daliang ^c   Li, Wen Hong ^c   Bugliani, Marco ^d   Marchetti, Piero ^d   Bosco, Domenico ^e   Piemonti, Lorenzo ^f   Johnson, Paul ^g   Hughes, Stephen J ^g   Rutter, Guy A ^a  

^a Section of Cell Biology   (United Kingdom)

^b UNIVERSITY OF GENEVA   (Switzerland)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^d UNIVERSITY OF PISA   (Italy)

^e GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^f SAN RAFFAELE HOSPITAL   (Italy)

^g UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EXENDIN 4; GASTRIC INHIBITORY POLYPEPTIDE; GLUCAGON LIKE PEPTIDE 1; INCRETIN; PALMITIC ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BODY MASS; CELL ACTIVITY; CELL POPULATION; CELL SUBPOPULATION; CELL SURFACE; CELL VIABILITY; CONTROLLED STUDY; GAP JUNCTION; GLUCOSE INTOLERANCE; HORMONE RELEASE; HUMAN; HUMAN CELL; IN VIVO STUDY; INSULIN RELEASE; LIPID DIET; LIPOTOXICITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SIGNAL TRANSDUCTION; UPREGULATION;

ANIMALS; BLOOD GLUCOSE; BODY MASS INDEX; CALCIUM SIGNALING; CELL COMMUNICATION; CELLS, CULTURED; DIABETES MELLITUS, TYPE 2; DIET, HIGH-FAT; FATTY ACIDS, NONESTERIFIED; GAP JUNCTIONS; GLUCAGON-LIKE PEPTIDE 1; GLUCOSE; HOMEOSTASIS; HUMANS; INCRETINS; INSULIN; INSULIN-SECRETING CELLS; MICE; MICE, INBRED C57BL; SPECIES SPECIFICITY;

EID: 84885047941     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI68459     Document Type: Article

References (72)

1. International Diabetes Federation. IDF Diabetes Atlas. 5th ed. Brussels, Belgium: International Diabetes Federation; 2011.
2. Prentki M, Nolan CJ. Islet beta cell failure in type 2 diabetes. J Clin Invest. 2006;116(7):1802-1812.
3. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52(9):1766-1777.
4. Stitt AW. AGEs and diabetic retinopathy. Invest Ophthalmol Vis Sci. 2010;51(10):4867-4874.
5. McCulloch LJ, van de Bunt M, Braun M, Frayn KN, Clark A, Gloyn AL. GLUT2 (SLC2A2) is not the principal glucose transporter in human pancreatic beta cells: implications for understanding genetic association signals at this locus. Mol Geneti Metab. 2011;104(4):648-653.
6. Tarasov AI, et al. The mitochondrial Ca2+ uniporter MCU is essential for glucose-induced ATP increases in pancreatic beta-cells. PLoS One. 2012;7(7):e39722.
7. Hattersley AT, Ashcroft FM. Activating mutations in Kir6. 2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy. Diabetes. 2005;54(9):2503-2513.
8. Grapengiesser E, Gylfe E, Hellman B. Dual effect of glucose on cytoplasmic Ca2+ in single pancreatic beta-cells. Biochem Biophys Res Commun. 1988;150(1):419-425.
9. Tsuboi T, Rutter GA. Multiple forms of "kissand-run" exocytosis revealed by evanescent wave microscopy. Curr Biol. 2003;13(7):563-567.
10. Henquin JC. The dual control of insulin secretion by glucose involves triggering and amplifying pathways in beta-cells. Diabetes Res Clin Pract. 2011;93(suppl 1):S27-S31.
11. Phillips LK, Prins JB. Update on incretin hormones. Ann N Y Acad Sci. 2011;1243:E55-E74.
12. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87(4):1409-1439.
13. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131-2157.
14. Seino Y, Fukushima M, Yabe D. GIP and GLP-1, the two incretin hormones: Similarities and differences. J Diabetes Invest. 2010;1(2):8-23.
15. Lamont BJ, Li Y, Kwan E, Brown TJ, Gaisano H, Drucker DJ. Pancreatic GLP-1 receptor activation is sufficient for incretin control of glucose metabolism in mice. J Clin Invest. 2012;122(1):388-402.
16. MacDonald PE, El-Kholy W, Riedel MJ, Salapatek AM, Light PE, Wheeler MB. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes. 2002;51(suppl 3):S434-S442.
17. Hansotia T, et al. Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. Diabetes. 2004;53(5):1326-1335.
18. Furman B, Ong WK, Pyne NJ. Cyclic AMP signaling in pancreatic islets. Adv Exp Med Biol. 2010;654:281-304.
19. Leech CA, et al. Molecular physiology of glucagon-like peptide-1 insulin secretagogue action in pancreatic beta cells. Prog Biophys Mol Biol. 2011;107(2):236-247.
20. Li Y, Hansotia T, Yusta B, Ris F, Halban PA, Drucker DJ. Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. J Biol Chem. 2003;278(1):471-478.
21. Garber AJ. Long-acting glucagon-like peptide 1 receptor agonists: a review of their efficacy and tolerability. Diabetes Care. 2011;34(suppl 2):S279-S284.
22. Kjems LL, Holst JJ, Volund A, Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes. 2003;52(2):380-386.
23. Hojberg PV, et al. 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(2):199-207.
24. Holst JJ, Knop FK, Vilsboll T, Krarup T, Madsbad S. Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes. Diabetes Care. 2011;34(suppl 2):S251-S257.
25. Knop FK, et al. Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diabetes Obes Metab. 2012;14(6):500-510.
26. Steiner DJ, Kim A, Miller K, Hara M. Pancreatic islet plasticity: interspecies comparison of islet architecture and composition. Islets. 2010;2(3):135-145.
27. Cabrera O, Berman DM, Kenyon NS, Ricordi C, Berggren PO, Caicedo A. The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci U S A. 2006;103(7):2334-2339.
28. Bosco D, et al. Unique arrangement of alpha- and beta-cells in human islets of Langerhans. Diabetes. 2010;59(5):1202-1210.
29. Rodriguez-Diaz R, et al. Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming beta cell function in humans. Nat Med. 2011;17(7):888-892.
30. Rodriguez-Diaz R, et al. Innervation patterns of autonomic axons in the human endocrine pancreas. Cell Metab. 2011;14(1):45-54.
31. Hodson DJ, et al. Existence of long-lasting experience-dependent plasticity in endocrine cell networks. Nat Commun. 2012;3:605.
32. Schlegel W, et al. Oscillations of cytosolic Ca2+ in pituitary cells due to action potentials. Nature. 1987;329(6141):719-721.
33. Rorsman P, Braun M, Zhang Q. Regulation of calcium in pancreatic alpha- and beta-cells in health and disease. Cell Calcium. 2012;51(3-4):300-308.
34. Quesada I, et al. Glucose induces opposite intracellular Ca2+ concentration oscillatory patterns in identified alpha- and beta-cells within intact human islets of Langerhans. Diabetes. 2006;55(9):2463-2469.
35. Serre-Beinier V, et al. Cx36 makes channels coupling human pancreatic beta-cells, and correlates with insulin expression. Hum Mol Genet. 2009;18(3):428-439.
36. Ravier MA, et al. Loss of connexin36 channels alters beta-cell coupling, islet synchronization of glucose-induced Ca2+ and insulin oscillations, and basal insulin release. Diabetes. 2005;54(6):1798-1807.
37. Head WS, Orseth ML, Nunemaker CS, Satin LS, Piston DW, Benninger RK. Connexin-36 gap junctions regulate in vivo first- and second-phase insulin secretion dynamics and glucose tolerance in the conscious mouse. Diabetes. 2012;61(7):1700-1707.
38. Zhang Q, et al. Cell coupling in mouse pancreatic beta-cells measured in intact islets of Langerhans. Philos Trans A Math Phys Eng Sci. 2008;366:3503-3523.
39. Li D, et al. Imaging dynamic insulin release using a fluorescent zinc indicator for monitoring induced exocytotic release (ZIMIR). Proc Natl Acad Sci U S A. 2011;108(52):21063-21068.
40. Maedler K, Oberholzer J, Bucher P, Spinas GA, Donath MY. Monounsaturated fatty acids prevent the deleterious effects of palmitate and high glucose on human pancreatic beta-cell turnover and function. Diabetes. 2003;52(3):726-733.
41. Poitout V. Beta-cell lipotoxicity: burning fat into heat? Endocrinology. 2004;145(8):3563-3565.
42. Muscelli E, et al. Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients. Diabetes. 2008;57(5):1340-1348.
43. Joseph JW, et al. Free fatty acid-induced beta-cell defects are dependent on uncoupling protein 2 expression. J Biol Chem. 2004;279(49):51049-51056.
44. Allagnat F, Alonso F, Martin D, Abderrahmani A, Waeber G, Haefliger JA. ICER-1gamma overexpression drives palmitate-mediated connexin36 down-regulation in insulin-secreting cells. J Biol Chem. 2008;283(9):5226-5234.
45. Mears D, Sheppard NF, Atwater I, Rojas E. Magnitude and modulation of pancreatic beta-cell gap junction electrical conductance in situ. J Membr Biol. 1995;146(2):163-176.
46. Ravier MA, Sehlin J, Henquin JC. Disorganization of cytoplasmic Ca (2+) oscillations and pulsatile insulin secretion in islets from ob/obmice. Diabetologia. 2002;45(8):1154-1163.
47. Zhang M, et al. Long lasting synchronization of calcium oscillations by cholinergic stimulation in isolated pancreatic islets. Biophys J. 2008;95(10):4676-4688.
48. Carvalho CP, et al. Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice. Am J Physiol Endocrinol Metab. 2012;303(1):E144-E151.
49. Winzell MS, Ahren B. The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes. 2004;53(suppl 3):S215-S219.
50. Miller MR, et al. Levels of free fatty acids (FFA) are associated with insulin resistance but do not explain the relationship between adiposity and insulin resistance in Hispanic Americans: the IRAS Family Study. J Clin Endocrinol Metab. 2012;97(9):3285-3291.
51. Knop FK, Aaboe K, Vilsboll T, Madsbad S, Krarup T, Holst JJ. Reduced incretin effect in obese subjects with normal glucose tolerance as compared to lean control subjects. Diabetologia. 2008;51:S258-S258.
52. Schafer SA, et al. Impaired glucagon-like peptide-1-induced insulin secretion in carriers of transcription factor 7-like 2 (TCF7L2) gene polymorphisms. Diabetologia. 2007;50(12):2443-2450.
53. Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001;50(3):609-613.
54. Houslay MD, Milligan G. Tailoring cAMP-signalling responses through isoform multiplicity. Trends Biochem Sci. 1997;22(6):217-224.
55. Dulin NO, Niu J, Browning DD, Ye RD, Voyno-Yasenetskaya T. Cyclic AMP-independent activation of protein kinase A by vasoactive peptides. J Biol Chem. 2001;276(24):20827-20830.
56. Ma Y, Pitson S, Hercus T, Murphy J, Lopez A, Woodcock J. Sphingosine activates protein kinase A type II by a novel cAMP-independent mechanism. J Biol Chem. 2005;280(28):26011-26017.
57. Hu W, Bielawski J, Samad F, Merrill AH, Cowart LA. Palmitate increases sphingosine-1-phosphate in C2C12 myotubes via upregulation of sphingosine kinase message and activity. J Lipid Res. 2009;50(9):1852-1862.
58. Tian G, Sandler S, Gylfe E, Tengholm A. Glucoseand hormone-induced cAMP oscillations in alphaand beta-cells within intact pancreatic islets. Diabetes. 2011;60(5):1535-1543.
59. Hoppa MB, et al. Chronic palmitate exposure inhibits insulin secretion by dissociation of Ca (2+) channels from secretory granules. Cell Metab. 2009;10:455-465.
60. Collins SC, et al. Progression of diet-induced diabetes in C57BL6J mice involves functional dissociation of Ca2 (+) channels from secretory vesicles. Diabetes. 2010;59(5):1192-1201.
61. Gehrmann W, Elsner M, Lenzen S. Role of metabolically generated reactive oxygen species for lipotoxicity in pancreatic beta-cells. Diabetes Obes Metab. 2010;12(suppl 2):149-158.
62. Benninger RK, Zhang M, Head WS, Satin LS, Piston DW. Gap junction coupling and calcium waves in the pancreatic islet. Biophys J. 2008;95(11):5048-5061.
63. Stozer A, et al. Functional connectivity in islets of Langerhans from mouse pancreas tissue slices. PLoS Comput Biol. 2013;9(2):e1002923.
64. Stozer A, Dolensek J, Rupnik MS. Glucose-stimulated calcium dynamics in islets of Langerhans in acute mouse pancreas tissue slices. PLoS One. 2013;8(1):e54638.
65. Ellacott KL, Morton GJ, Woods SC, Tso P, Schwartz MW. Assessment of feeding behavior in laboratory mice. Cell Metab. 2010;12(1):10-17.
66. Hodson DJ, et al. Coordination of calcium signals by pituitary endocrine cells in situ. Cell Calcium. 2012;51(3-4):222-230.
67. Kang ZF, et al. 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(2):423-433.
68. Marchetti P, et al. A local glucagon-like peptide 1 (GLP-1) system in human pancreatic islets. Diabetologia. 2012;55(12):3262-3272.
69. Panjwani N, et al. GLP-1 receptor activation indirectly reduces hepatic lipid accumulation but does not attenuate development of atherosclerosis in diabetic male ApoE (-/-) mice. Endocrinology. 2013;154(1):127-139.
70. Rocheleau JV, et al. Critical role of gap junction coupled KATP channel activity for regulated insulin secretion. PLoS Biology. 2006;4(2):e26.
71. Ravier MA, Rutter GA. Glucose or insulin, but not zinc ions, inhibit glucagon secretion from mouse pancreatic alpha-cells. Diabetes. 2005;54(6):1789-1797.
72. Sanchez-Cardenas C, et al. Pituitary growth hormone network responses are sexually dimorphic and regulated by gonadal steroids in adulthood. Proc Natl Acad Sci U S A. 2010;107(50):21878-21883.