References

1. Cooper ME, El-Osta A. Epigenetics: mechanisms and implications for diabetic complications. Circ Res. 2010;107(12):1403-1413.
2. Mutskov V, Felsenfeld G. The human insulin gene is part of a large open chromatin domain specific for human islets. Proc Natl Acad Sci U S A. 2009;106(41):17419-17424.
3. Xu Z et al. Mapping of INS promoter interactions reveals its role in long-range regulation of SYT8 transcription. Nat Struct Mol Biol. 2011;18(3):372-378.
4. Jensen CB et al. Altered PI3-kinase/Akt signalling in skeletal muscle of young men with low birth weight. PLoS One. 2008;3(11):e3738.
5. Sandovici I et al. Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets. Proc Natl Acad Sci U S A. 2011;108:5449-5454.
6. Roggli E et al. Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic β-cells. Diabetes. 2012;61(7):1742-1751.
7. Roggli E et al. Changes in microRNA expression contribute to pancreatic β-cell dysfunction in prediabetic NOD Mice. Diabetes. 2012;61(7):1742-1751.
8. Giannini C et al. Evidence for early defects in insulin sensitivity and secretion before the onset of glucose dysregulation in obese youths: a longitudinal study. Diabetes. 2012;61(3):606-614.
9. Florez JC. Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: where are the insulin resistance genes? Diabetologia. 2008;51(7):1100-1110.
10. Müssig K et al. Genetic variants affecting incretin sensitivity and incretin secretion. Diabetologia. 2010;53(11):2289-2297.
11. Stolerman ES et al. TCF7L2 variants are associated with increased proinsulin/insulin ratios but not obesity traits in the Framingham Heart Study. Diabetologia. 2009;52(4):614-620.
12. Florez JC et al. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med. 2006;355:241-250.
13. Qiu L et al. Differentially expressed proteins in the pancreas of diet-induced diabetic mice. Mol Cell Proteomics. 2005;4:1311-1318.
14. Dreja T et al. Diet-induced gene expression of isolated pancreatic islets from a polygenic mouse model of the metabolic syndrome. Diabetologia. 2010;53(2):309-320.
15. Dokmanovic-Chouinard M et al. Positional cloning of “Lisch-Like”, a candidate modifier of susceptibility to type 2 diabetes in mice. PLoS Genet. 2008;4(7):e1000137.
16. Potter KJ et al. Islet amyloid deposition limits the viability of human islet grafts but not porcine islet grafts. Proc Natl Acad Sci U S A. 2010;107(9):4305-4310.
17. Westwell-Roper C et al. IL-1 blockade attenuates islet amyloid polypeptide-induced proinflammatory cytokine release and pancreatic islet graft dysfunction. J Immunol. 2011;187(5):2755-2765.
18. Bouzakri K et al. Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle. Diabetes. 2011;60(4):1111-1121.
19. Kassem SA et al. β-Cell proliferation and apoptosis in the normal fetal and neonatal human pancreas and in persistent hyperinsulinemic hypoglycemia of infancy (PHHI). Diabetes. 2000;49(8):1325-1333.
20. Remedi MS, Nichols CG. Hyperinsulinism and diabetes: genetic dissection of β-cell metabolism-excitation coupling in mice. Cell Metab. 2009;10(6):442-453.
21. Remedi MS et al. Secondary consequences of β-cell inexcitability: identification and prevention in a murine model of KATP-induced neonatal diabetes mellitus. Cell Metab. 2009;9(2):140-151.
22. Drews G et al. Oxidative stress and beta-cell dysfunction. Pflugers Arch. 2010;460(4):703-718.
23. Gier B et al. Suppression of KATP channel activity protects murine pancreatic β cells against oxidative stress. J Clin Invest. 2009;119(11):3246-3256.
24. Herchuelz A et al. Na/Ca exchange and Ca2+ homeostasis in the pancreatic beta-cell. Diabetes Metab. 2002;28(6, pt 2):3S54-3S60; discussion 3S108-3S112.
25. Nguidjoe E et al. Heterozygous inactivation of the Na/Ca exchanger increases glucose-induced insulin release, β-cell proliferation, and mass. Diabetes. 2011;60(8):2076-2085.
26. Kassem S et al. Large islets, beta-cell proliferation, and a glucokinase mutation. N Engl J Med. 2010;362(14):1348-1350.
27. Porat S et al. Control of pancreatic β cell regeneration by glucose metabolism. Cell Metab. 2011;13(4):440-449.
28. Braun M et al. Gamma-aminobutyric acid (GABA) is an autocrine excitatory transmitter in human pancreatic β cells. Diabetes. 2010;59(7):1694-1701.
29. Jacques-Silva MC et al. ATP-gated P2X3 receptors constitute a positive autocrine signal for insulin release in the human pancreatic β cell. Proc Natl Acad Sci U S A. 2010;107:6465-6470.
30. Wijesekara N et al. Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion. Diabetologia. 2010;53:1656-1668.
31. Bouche C et al. Insulin enhances glucose-stimulated insulin secretion in healthy humans. Proc Natl Acad Sci U S A. 2010;107:4770-4775.
32. Lopez X et al. Exogenous insulin enhances glucose-stimulated insulin response in healthy humans independent of changes in free fatty acids. J Clin Endocrinol Metab. 2011;96(12):3811-3821.
33. Halperin F et al. Insulin augmentation of glucose-stimulated insulin secretion is impaired in insulin-resistant humans. Diabetes. 2012;61(2):301-309.
34. Retnakaran R et al. Initial short-term intensive insulin therapy as a strategy for evaluating the preservation of beta-cell function with oral antidiabetic medications: a pilot study with sitagliptin. Diabetes Obes Metab. 2010;12(10):909-915.
35. Opsteen C et al. Effect of short-term intensive insulin therapy on quality of life in type 2 diabetes. J Eval Clin Pract. 2012;18(2):256-261.

The hyperstimulated β cell: prelude to diabetes?
I- What is the role of epigenetics in insulin gene expression and insulin secretion and action
II- Impact of insulin resistance on β-cell function
III- Intrinsic hyperstimulation of β-cells
IV- Modulation of β-cell function by secretory products
V- Conclusion
Lectures during IGIS meeting
References