Selective inhibition of 12-lipoxygenase protects islets and beta cells from inflammatory cytokine-mediated beta cell dysfunction

Diabetologia

Volumn 58, Issue 3, 2015, Pages 549-557

  Taylor Fishwick, David A ^a   Weaver, Jessica ^a   Glenn, Lindsey ^a   Kuhn, Norine ^a   Rai, Ganesha ^b   Jadhav, Ajit ^b   Simeonov, Anton ^b   Dudda, Angela ^c   Schmoll, Dieter ^d   Holman, Theodore R ^e   Maloney, David J ^b   Nadler, Jerry L ^a  

^a EASTERN VIRGINIA MEDICAL SCHOOL   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

^c Process Development Biotechnology   (Germany)

^d Diabetes Division   (Germany)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

12 Lipoxygenase; Cytokines; Diabetes; Drug discovery; Inhibitors; Islets

Indexed keywords

12 HYDROXYICOSATETRAENOIC ACID; ARACHIDONATE 12 LIPOXYGENASE; CASPASE 3; GAMMA INTERFERON; GLUCOSE; INSULIN; INTERLEUKIN 12P40; INTERLEUKIN 1BETA; MCP1 PROTEIN; OXYGENASE INHIBITOR; PROTEIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; ENZYME INHIBITOR;

ANIMAL CELL; ANIMAL EXPERIMENT; APOPTOSIS; ARTICLE; CELL DEATH; CELL SURVIVAL; COCULTURE; CONTROLLED STUDY; DRUG BLOOD LEVEL; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME LINKED IMMUNOSORBENT ASSAY; FATTY ACID BLOOD LEVEL; FLUORESCENCE MICROSCOPY; GENE EXPRESSION; HUMAN; HUMAN CELL; INFLAMMATION; INSULIN RELEASE; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PANCREAS ISLET BETA CELL; PANCREAS ISLET CELL FUNCTION; PLASMA HALF LIFE; PRIORITY JOURNAL; RAT; UPREGULATION; ANIMAL; C57BL MOUSE; CELL LINE; DRUG EFFECTS; IN VITRO STUDY; METABOLISM; REAL TIME POLYMERASE CHAIN REACTION;

12-HYDROXY-5,8,10,14-EICOSATETRAENOIC ACID; ANIMALS; APOPTOSIS; ARACHIDONATE 12-LIPOXYGENASE; CELL LINE; CELL SURVIVAL; ENZYME INHIBITORS; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; IN VITRO TECHNIQUES; INSULIN-SECRETING CELLS; INTERLEUKIN-1BETA; MALE; MICE; MICE, INBRED C57BL; REAL-TIME POLYMERASE CHAIN REACTION; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84925483027     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-014-3452-0     Document Type: Article

References (38)

1. Donath MY (2014) Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug Discov 13:465–476
2. Soleimanpour SA, Stoffers DA (2013) The pancreatic beta cell and type 1 diabetes: innocent bystander or active participant? Trends Endocrinol Metab 24:324–331
3. Westwell-Roper C, Ehses JA (2014) Is there a role for the adaptive immune system in pancreatic beta cell failure in type 2 diabetes? Diabetologia 57:447–450
4. Ehses JA, Perren A, Eppler E et al (2007) Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56:2356–2370
5. Eizirik DL, Sammeth M, Bouckenooghe T et al (2012) The human pancreatic islet transcriptome: expression of candidate genes for type 1 diabetes and the impact of pro-inflammatory cytokines. PLoS Genet 8:e1002552
6. Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115:1111–1119
7. Tersey SA, Nishiki Y, Templin AT et al (2012) Islet beta-cell endoplasmic reticulum stress precedes the onset of type 1 diabetes in the nonobese diabetic mouse model. Diabetes 61:818–827
8. Arif S, Moore F, Marks K et al (2011) Peripheral and islet interleukin-17 pathway activation characterizes human autoimmune diabetes and promotes cytokine-mediated beta-cell death. Diabetes 60:2112–2119
9. Atkinson MA, Eisenbarth GS, Michels AW (2014) Type 1 diabetes. Lancet 383:69–82
10. Baldwin AC, Green CD, Olson LK, Moxley MA, Corbett JA (2012) A role for aberrant protein palmitoylation in FFA-induced ER stress and beta-cell death. Am J Physiol Endocrinol Metab 302:E1390–E1398
11. Imai Y, Dobrian AD, Weaver JR et al (2013) Interaction between cytokines and inflammatory cells in islet dysfunction, insulin resistance and vascular disease. Diabetes Obes Metab 15(Suppl 3):117–129
12. Moran A, Bundy B, Becker DJ et al (2013) Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet 381:1905–1915
13. Weaver JR, Holman TR, Imai Y et al (2012) Integration of pro-inflammatory cytokines, 12-lipoxygenase and NOX-1 in pancreatic islet beta cell dysfunction. Mol Cell Endocrinol 358:88–95
14. Brash AR (1999) Lipoxygenases: occurrence, functions, catalysis, and acquisition of substrate. J Biol Chem 274:23679–23682
15. Dobrian AD, Lieb DC, Cole BK, Taylor-Fishwick DA, Chakrabarti SK, Nadler JL (2011) Functional and pathological roles of the 12- and 15-lipoxygenases. Prog Lipid Res 50:115–131
16. Ma K, Nunemaker CS, Wu R, Chakrabarti SK, Taylor-Fishwick DA, Nadler JL (2010) 12-Lipoxygenase products reduce insulin secretion and {beta}-cell viability in human islets. J Clin Endocrinol Metab 95:887–893
17. McDuffie M, Maybee NA, Keller SR et al (2008) Nonobese diabetic (NOD) mice congenic for a targeted deletion of 12/15-lipoxygenase are protected from autoimmune diabetes. Diabetes 57:199–208
18. Shannon VR, Ramanadham S, Turk J, Holtzman MJ (1992) Selective expression of an arachidonate 12-lipoxygenase by pancreatic islet beta-cells. Am J Physiol 263:E828–E836
19. Chen M, Yang ZD, Smith KM, Carter JD, Nadler JL (2005) Activation of 12-lipoxygenase in proinflammatory cytokine-mediated beta cell toxicity. Diabetologia 48:486–495
20. Laybutt DR, Sharma A, Sgroi DC, Gaudet J, Bonner-Weir S, Weir GC (2002) Genetic regulation of metabolic pathways in beta-cells disrupted by hyperglycemia. J Biol Chem 277:10912–10921
21. Ma Z, Ramanadham S, Corbett JA et al (1996) Interleukin-1 enhances pancreatic islet arachidonic acid 12-lipoxygenase product generation by increasing substrate availability through a nitric oxide-dependent mechanism. J Biol Chem 271:1029–1042
22. Natarajan R, Gu JL, Rossi J et al (1993) Elevated glucose and angiotensin II increase 12-lipoxygenase activity and expression in porcine aortic smooth muscle cells. Proc Natl Acad Sci U S A 90:4947–4951
23. Green-Mitchell SM, Tersey SA, Cole BK et al (2013) Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development. PLoS One 8:e56763
24. Nunemaker CS, Chen M, Pei H et al (2008) 12-Lipoxygenase-knockout mice are resistant to inflammatory effects of obesity induced by Western diet. Am J Physiol Endocrinol Metab 295:E1065–E1075
25. Sears DD, Miles PD, Chapman J et al (2009) 12/15-Lipoxygenase is required for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice. PLoS One 4:e7250
26. Cole BK, Morris MA, Grzesik WJ, Leone KA, Nadler JL (2012) Adipose tissue-specific deletion of 12/15-lipoxygenase protects mice from the consequences of a high-fat diet. Mediat Inflamm 2012:851798
27. Taylor-Fishwick DA, Weaver JR, Grzesik W et al (2013) Production and function of IL-12 in islets and beta cells. Diabetologia 56:126–135
28. Kenyon V, Rai G, Jadhav A et al (2011) Discovery of potent and selective inhibitors of human platelet-type 12- lipoxygenase. J Med Chem 54:5485–5497
29. Carter JD, Dula SB, Corbin KL, Wu R, Nunemaker CS (2009) A practical guide to rodent islet isolation and assessment. Biol Proced Online 11:3–31
30. Cozar-Castellano I, Harb G, Selk K et al (2008) Lessons from the first comprehensive molecular characterization of cell cycle control in rodent insulinoma cell lines. Diabetes 57:3056–3068
31. Weaver JR, Taylor-Fishwick DA (2013) Regulation of NOX-1 expression in beta cells: a positive feedback loop involving the Src-kinase signaling pathway. Mol Cell Endocrinol 369:35–41
32. Ullman-Cullere MH, Foltz CJ (1999) Body condition scoring: a rapid and accurate method for assessing health status in mice. Lab Anim Sci 49:319–323
33. Bleich D, Chen S, Zipser B, Sun D, Funk CD, Nadler JL (1999) Resistance to type 1 diabetes induction in 12-lipoxygenase knockout mice. J Clin Invest 103:1431–1436
34. Imai Y, Morris MA, Dobrian AD, Taylor-Fishwick DA, Nadler JL (2013) Inflammatory pathways linked to beta cell demise in diabetes. In: Islam S (ed) The islets of Langerhans, 2nd edn. Springer, Dordrecht
35. Tersey SA, Maier B, Nishiki Y, Maganti AV, Nadler JL, Mirmira RG (2014) 12-Lipoxygenase promotes obesity-induced oxidative stress in pancreatic islets. Mol Cell Biol 34:3735–3745
36. Deschamps JD, Kenyon VA, Holman TR (2006) Baicalein is a potent in vitro inhibitor against both reticulocyte 15-human and platelet 12-human lipoxygenases. Bioorg Med Chem 14:4295–4301
37. Zhao L, Cuff CA, Moss E et al (2002) Selective interleukin-12 synthesis defect in 12/15-lipoxygenase-deficient macrophages associated with reduced atherosclerosis in a mouse model of familial hypercholesterolemia. J Biol Chem 277:35350–35356
38. Luci DK, Jameson JB 2nd, Yasgar A et al (2014) Synthesis and structure-activity relationship studies of 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase. J Med Chem 57:495–506