Some cannabinoid receptor ligands and their distomers are direct-acting openers of SUR1 K ATP channels

American Journal of Physiology - Endocrinology and Metabolism

Volumn 302, Issue 5, 2012, Pages

  Lynch, Christopher J ^a   Zhou, Qing ^b   Shyng, Show Ling ^b   Heal, David J ^c   Cheetham, Sharon C ^c   Dickinson, Keith ^c   Gregory, Peter ^d   Firnges, Michael ^e   Nordheim, Ulrich ^d   Goshorn, Stephanie ^a   Reiche, Dania ^e   Turski, Lechoslaw ^d   Antel, Jochen ^d  

^a PENN STATE COLLEGE OF MEDICINE   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^c RenaSci Ltd   (United Kingdom)

^d ABBOTT GMBH AND CO KG   (Germany)

^e BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

ATP sensitive potassium channels; Diazoxide; Glibenclamide; Glucose stimulated insulin secretion; Insulin; Oral glucose tolerance; Sulfonylurea receptor 1; Zucker rat

Indexed keywords

DIAZOXIDE; IBIPINABANT; INSULIN; RIMONABANT; SULFONYLUREA RECEPTOR 1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BODY WEIGHT; CHANNEL GATING; CONTROLLED STUDY; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; FOLLOW UP; GLUCOSE INTOLERANCE; GLUCOSE STIMULATED INSULIN SECRETION; GLUCOSE TOLERANCE; HYPERINSULINEMIA; IN VITRO STUDY; IN VIVO STUDY; INSULIN RELEASE; MALE; NONHUMAN; PRIORITY JOURNAL; RAT;

ALLOSTERIC REGULATION; ANIMALS; ANTI-OBESITY AGENTS; ATP-BINDING CASSETTE TRANSPORTERS; CELL LINE, TRANSFORMED; CERCOPITHECUS AETHIOPS; CRICETINAE; GLUCOSE INTOLERANCE; HUMANS; HYPOGLYCEMIC AGENTS; ISLETS OF LANGERHANS; LIGANDS; MALE; MEMBRANE TRANSPORT MODULATORS; MICE; MICE, KNOCKOUT; MICE, OBESE; POTASSIUM CHANNELS, INWARDLY RECTIFYING; RATS; RATS, ZUCKER; RECEPTOR, CANNABINOID, CB1; RECEPTORS, DRUG; RECOMBINANT PROTEINS; STEREOISOMERISM;

EID: 84857283869     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00250.2011     Document Type: Article

References (82)

1. Alemzadeh R, Fledelius C, Bodvarsdottir T, Sturis J. Attenuation of hyperinsulinemia by NN414, a SUR1/Kir6.2 selective K-adenosine triphosphate channel opener, improves glucose tolerance and lipid profile in obese Zucker rats. Metabolism 53: 441-447, 2004.
2. Alemzadeh R, Holshouser S. Effect of diazoxide on brain capillary insulin receptor binding and food intake in hyperphagic obese Zucker rats. Endocrinology 140: 3197-3202, 1999.
3. Alemzadeh R, Holshouser S, Massey P, Koontz J. Chronic suppression of insulin by diazoxide alters the activities of key enzymes regulating hepatic gluconeogenesis in Zucker rats. Eur J Endocrinol 146: 871-879, 2002.
4. Alemzadeh R, Jacobs W, Pitukcheewanont P. Antiobesity effect of diazoxide in obese Zucker rats. Metabolism 45: 334-341, 1996.
5. Alemzadeh R, Karlstad MD, Tushaus K, Buchholz M. Diazoxide enhances basal metabolic rate and fat oxidation in obese Zucker rats. Metabolism 57: 1597-1607, 2008.
6. Alemzadeh R, Slonim AE, Zdanowicz MM, Maturo J. Modification of insulin resistance by diazoxide in obese Zucker rats. Endocrinology 133: 705-712, 1993.
7. Alemzadeh R, Tushaus K. Diazoxide attenuates insulin secretion and hepatic lipogenesis in zucker diabetic fatty rats. Med Sci Monit 11: BR439-BR448, 2005.
8. Alemzadeh R, Tushaus KM. Modulation of adipoinsular axis in prediabetic zucker diabetic fatty rats by diazoxide. Endocrinology 145: 5476-5484, 2004.
9. Alemzadeh R, Zhang J, Tushaus K, Koontz J. Diazoxide enhances adipose tissue protein kinase B activation and glucose transporter-4 expression in obese Zucker rats. Med Sci Monit 10: BR53-BR60, 2004.
10. Bermudez-Silva FJ, Sanchez-Vera I, Suárez J, Serrano A, Fuentes E, Juan-Pico P, Nadal A, Rodríguez de Fonseca F. Role of cannabinoid CB2 receptors in glucose homeostasis in rats. Eur J Pharmacol 565: 207-211, 2007.
11. Bermúdez-Silva FJ, Suárez J, Baixeras E, Cobo N, Bautista D, Cuesta-Muñoz AL, Fuentes E, Juan-Pico P, Castro MJ, Milman G, Mechoulam R, Nadal A, Rodríguez de Fonseca F. Presence of functional cannabinoid receptors in human endocrine pancreas. Diabetologia 51: 476-487, 2008.
12. Bermúdez-Siva FJ, Serrano A, Diaz-Molina FJ, Sánchez Vera I, Juan-Pico P, Nadal A, Fuentes E, Rodríguez de Fonseca F. Activation of cannabinoid CB1 receptors induces glucose intolerance in rats. Eur J Pharmacol 531: 282-284, 2006.
13. Björk E, Berne C, Kämpe O, Wibell L, Oskarsson P, Karlsson FA. Diazoxide treatment at onset preserves residual insulin secretion in adults with autoimmune diabetes. Diabetes 45: 1427-1430, 1996.
14. Björk E, Berne C, Karlsson FA. Induction of beta-cell rest in type 1 diabetes. Studies on the effects of octreotide and diazoxide. Diabetes Care 21: 427-430, 1998.
15. Björklund A, Bondo Hansen J, Falkmer S, Grill V. Openers of ATP-dependent K-channels protect against a signal-transduction-linked and not freely reversible defect of insulin secretion in a rat islet transplantation model of Type 2 diabetes. Diabetologia 47: 885-891, 2004.
16. Carr RD, Brand CL, Bodvarsdottir TB, Hansen JB, Sturis J. NN414, a SUR1/Kir6.2-selective potassium channel opener, reduces blood glucose and improves glucose tolerance in the VDF Zucker rat. Diabetes 52: 2513-2518, 2003.
17. Corkey BE. Banting lecture 2011: hyperinsulinemia: cause or consequence? Diabetes 61: 4-13, 2012.
18. Dabrowski M, Ashcroft FM, Ashfield R, Lebrun P, Pirotte B, Egebjerg J, Bondo Hansen J, Wahl P. The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener. Diabetes 51: 1896-1906, 2002.
19. Dabrowski M, Larsen T, Ashcroft FM, Bondo Hansen J, Wahl P. Potent and selective activation of the pancreatic beta-cell type K(ATP) channel by two novel diazoxide analogues. Diabetologia 46: 1375-1382, 2003.
20. Desai NM, Goss JA, Deng S, Wolf BA, Markmann E, Palanjian M, Shock AP, Feliciano S, Brunicardi FC, Barker CF, Naji A, Markmann JF. Elevated portal vein drug levels of sirolimus and tacrolimus in islet transplant recipients: local immunosuppression or islet toxicity? Transplantation 76: 1623-1625, 2003.
21. Di Marzo V, Despres JP. CB1 antagonists for obesity-what lessons have we learned from rimonabant? Nat Rev Endocrinol 5: 633-638, 2009.
22. Dickinson K, North TJ, Sills S, Anthony DM, Lock JI, Vowles DT, Jones RB. BTS 67 582 stimulates insulin secretion from perifused rat pancreatic islets. Eur J Pharmacol 339: 69-76, 1997.
23. Doyle ME. The role of the endocannabinoid system in islet biology. Curr Opin Endocrinol Diabetes Obes 18: 153-158, 2011.
24. Due A, Flint A, Eriksen G, Møller B, Raben A, Hansen JB, Astrup A. No effect of inhibition of insulin secretion by diazoxide on weight loss in hyperinsulinaemic obese subjects during an 8-week weight-loss diet. Diabetes Obes Metab 9: 566-574, 2007.
25. Duvivier VF, Delafoy-Plasse L, Delion V, Lechevalier P, Le Bail JC, Guillot E, Pruniaux MP, Galzin AM. Beneficial effect of a chronic treatment with rimonabant on pancreatic function and beta-cell morphology in Zucker Fatty rats. Eur J Pharmacol 616: 314-320, 2009.
26. Getty-Kaushik L, Richard AM, Deeney JT, Krawczyk S, Shirihai O, Corkey BE. The CB1 antagonist rimonabant decreases insulin hypersecretion in rat pancreatic islets. Obesity (Silver Spring) 17: 1856-1860, 2009.
27. Gey GO, Gey MK. The maintenance of human normal cells and tumor cells in continuous culture. I. Preliminary report: cultivation of mesoblastic tumors and normal tissue and notes on methods of cultivation. Am J Cancer 27: 45-76, 1936.
28. Grill V, Björklund A. Impact of metabolic abnormalities for beta cell function: clinical significance and underlying mechanisms. Mol Cell Endocrinol 297: 86-92, 2009.
29. Grill V, Radtke M, Qvigstad E, Kollind M, Björklund A. Beneficial effects of K-ATP channel openers in diabetes: an update on mechanisms and clinical experiences. Diabetes Obes Metab 11, Suppl 4: 143-148, 2009.
30. Guldstrand M, Grill V, Björklund A, Lins PE, Adamson U. Improved beta cell function after short-term treatment with diazoxide in obese subjects with type 2 diabetes. Diabetes Metab 28: 448-456, 2002.
31. Guo Z, Bu S, Yu Y, Ghatnekar G, Wang M, Chen L, Bu M, Yang L, Zhu B, Feng Z, Huang Q. Diazoxide prevents abdominal adiposity and fatty liver in obese OLETF rats at prediabetic stage. J Diabetes Complications 22: 46-55, 2008.
32. Ham MT, De Jong Y. Effects of delta-9-tetrahydrocannabinol and cannabidiol on blood glucose concentrations in rabbits and rat. Pharm Weekbl 110: 1157-1161, 1975.
33. Hansen JB. Towards selective Kir6.2/SUR1 potassium channel openers, medicinal chemistry and therapeutic perspectives. Curr Med Chem 13: 361-376, 2006.
34. Hansen JB, Arkhammar PO, Bodvarsdottir TB, Wahl P. Inhibition of insulin secretion as a new drug target in the treatment of metabolic disorders. Curr Med Chem 11: 1595-1615, 2004.
35. Hensley IE, Lawler JE, Alemzadeh R, Holshouser SJ. Diazoxide effects on hypothalamic and extra-hypothalamic NPY content in Zucker rats. Peptides 22: 899-908, 2001.
36. Hollister LE, Reaven GM. Delta-9-tetrahydrocannabinol and glucose tolerance. Clin Pharmacol Ther 16: 297-302, 1974.
37. Huang Q, Bu S, Yu Y, Guo Z, Ghatnekar G, Bu M, Yang L, Lu B, Feng Z, Liu S, Wang F. Diazoxide prevents diabetes through inhibiting pancreatic beta-cells from apoptosis via Bcl-2/Bax rate and p38-beta mitogen-activated protein kinase. Endocrinology 148: 81-91, 2007.
38. Izzo AA, Piscitelli F, Capasso R, Aviello G, Romano B, Borrelli F, Petrosino S, Di Marzo V. Peripheral endocannabinoid dysregulation in obesity: relation to intestinal motility and energy processing induced by food deprivation and re-feeding. Br J Pharmacol 158: 451-461, 2009.
39. Jetton TL, Lausier J, LaRock K, Trotman WE, Larmie B, Habibovic A, Peshavaria M, Leahy JL. Mechanisms of compensatory beta-cell growth in insulin-resistant rats: roles of Akt kinase. Diabetes 54: 2294-2304, 2005.
40. Jones D. End of the line for cannabinoid receptor 1 as an anti-obesity target? Nat Rev Drug Discov 7: 961-962, 2008.
41. Kullin M, Li Z, Hansen JB, Björk E, Sandler S, Karlsson FA. K(ATP) channel openers protect rat islets against the toxic effect of streptozotocin. Diabetes 49: 1131-1136, 2000.
42. Leahy JL, Bumbalo LM, Chen C. Diazoxide causes recovery of betacell glucose responsiveness in 90% pancreatectomized diabetic rats. Diabetes 43: 173-179, 1994.
43. Li C, Bowe JE, Huang GC, Amiel SA, Jones PM, Persaud SJ. Cannabinoid receptor agonists and antagonists stimulate insulin secretion from isolated human islets of Langerhans. Diabetes Obes Metab 13: 903-910, 2011.
44. Ma Z, Portwood N, Brodin D, Grill V, Björklund A. Effects of diazoxide on gene expression in rat pancreatic islets are largely linked to elevated glucose and potentially serve to enhance beta-cell sensitivity. Diabetes 56: 1095-1106, 2007.
45. Matias I, Cristino L, Di Marzo V. Endocannabinoids: some like it fat (and sweet too). J Neuroendocrinol 20, Suppl 1: 100-109, 2008.
46. Matias I, Gonthier MP, Orlando P, Martiadis V, De Petrocellis L, Cervino C, Petrosino S, Hoareau L, Festy F, Pasquali R, Roche R, Maj M, Pagotto U, Monteleone P, Di Marzo V. Regulation, function, and dysregulation of endocannabinoids in models of adipose and beta-pancreatic cells and in obesity and hyperglycemia. J Clin Endocrinol Metab 91: 3171-3180, 2006.
47. Matsuda M, Kawasaki F, Mikami Y, Takeuchi Y, Saito M, Eto M, Kaku K. Rescue of beta-cell exhaustion by diazoxide after the development of diabetes mellitus in rats with streptozotocin-induced diabetes. Eur J Pharmacol 453: 141-148, 2002.
48. Nielsen FE, Ebdrup S, Jensen AF, Ynddal L, Bodvarsdottir TB, Stidsen C, Worsaae A, Boonen HC, Arkhammar PO, Fremming T, Wahl P, Kornø HT, Hansen JB. New 3-alkylamino-4H-thieno-1,2,4-thiadiazine 1,1-dioxide derivatives activate ATP-sensitive potassium channels of pancreatic beta cells. J Med Chem 49: 4127-4139, 2006.
49. Nogueiras R, Veyrat-Durebex C, Suchanek PM, Klein M, Tschöp J, Caldwell C, Woods SC, Wittmann G, Watanabe M, Liposits Z, Fekete C, Reizes O, Rohner-Jeanrenaud F, Tschöp MH. Peripheral, but not central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats. Diabetes 57: 2977-2991, 2008.
50. O'Hare JD, Zielinski E, Cheng B, Scherer T, Buettner C. Central endocannabinoid signaling regulates hepatic glucose production and systemic lipolysis. Diabetes 60: 1055-1062, 2011.
51. Ortqvist E, Björk E, Wallensteen M, Ludvigsson J, Aman J, Johansson C, Forsander G, Lindgren F, Berglund L, Bengtsson M, Berne C, Persson B, Karlsson FA. Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes. Diabetes Care 27: 2191-2197, 2004.
52. Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S, Bátkai S, Harvey-White J, Mackie K, Offertáler L, Wang L, Kunos G. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 115: 1298-1305, 2005.
53. Oz M, Yang KH, Dinc M, Shippenberg TS. The endogenous cannabinoid anandamide inhibits cromakalim-activated K currents in follicleenclosed Xenopus oocytes. J Pharmacol Exp Ther 323: 547-554, 2007.
54. Panten U, Schwanstecher M, Schwanstecher C. Sulfonylurea receptors and mechanism of sulfonylurea action. Exp Clin Endocrinol Diabetes 104: 1-9, 1996.
55. Qvigstad E, Kollind M, Grill V. Nine weeks of bedtime diazoxide is well tolerated and improves beta-cell function in subjects with Type 2 diabetes. Diabet Med 21: 73-76, 2004.
56. Radtke M, Kollind M, Qvigstad E, Grill V. Twelve weeks' treatment with diazoxide without insulin supplementation in Type 2 diabetes is feasible but does not improve insulin secretion. Diabet Med 24: 172-177, 2007.
57. Radtke MA, Nermoen I, Kollind M, Skeie S, Sørheim JI, Svartberg J, Hals I, Moen T, Dørflinger GH, Grill V. Six months of diazoxide treatment at bedtime in newly diagnosed subjects with type 1 diabetes does not influence parameters of {beta}-cell function and autoimmunity but improves glycemic control. Diabetes Care 33: 589-594, 2010.
58. Rasmussen SB, Sørensen TS, Hansen JB, Mandrup-Poulsen T, Hornum L, Markholst H. Functional rest through intensive treatment with insulin and potassium channel openers preserves residual beta-cell function and mass in acutely diabetic BB rats. Horm Metab Res 32: 294-300, 2000.
59. Ritzel RA, Hansen JB, Veldhuis JD, Butler PC. Induction of beta-cell rest by a Kir6.2/SUR1-selective K(ATP)-channel opener preserves betacell insulin stores and insulin secretion in human islets cultured at high (11 mM) glucose. J Clin Endocrinol Metab 89: 795-805, 2004.
60. Scheen AJ, Van Gaal LG, Després JP, Pi-Sunyer X, Golay A, Hanotin C. [Rimonabant improves cardiometabolic risk profile in obese or overweight subjects: overview of RIO studies]. Rev Med Suisse 2: 1916-1923, 2006.
61. Schwanstecher M, Brandt C, Behrends S, Schaupp U, Panten U. Effect of MgATP on pinacidil-induced displacement of glibenclamide from the sulphonylurea receptor in a pancreatic beta-cell line and rat cerebral cortex. Br J Pharmacol 106: 295-301, 1992.
62. Schwanstecher M, Löser S, Brandt C, Scheffer K, Rosenberger F, Panten U. Adenine nucleotide-induced inhibition of binding of sulphonylureas to their receptor in pancreatic islets. Br J Pharmacol 105: 531-534, 1992.
63. Schwanstecher M, Löser S, Rietze I, Panten U. Phosphate and thiophosphate group donating adenine and guanine nucleotides inhibit glibenclamide binding to membranes from pancreatic islets. Naunyn Schmiedebergs Arch Pharmacol 343: 83-89, 1991.
64. Schwanstecher M, Schwanstecher C, Dickel C, Chudziak F, Moshiri A, Panten U. Location of the sulphonylurea receptor at the cytoplasmic face of the beta-cell membrane. Br J Pharmacol 113: 903-911, 1994.
65. Schwanstecher M, Sieverding C, Dörschner H, Gross I, Aguilar- Bryan L, Schwanstecher C, Bryan J. Potassium channel openers require ATP to bind to and act through sulfonylurea receptors. EMBO J 17: 5529-5535, 1998.
66. Seghers V, Nakazaki M, DeMayo F, Aguilar-Bryan L, Bryan J. Sur1 knockout mice. A model for K(ATP) channel-independent regulation of insulin secretion. J Biol Chem 275: 9270-9277, 2000.
67. She P, Reid TM, Bronson SK, Vary TC, Hajnal A, Lynch CJ, Hutson SM. Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab 6: 181-194, 2007.
68. Skak K, Gotfredsen CF, Lundsgaard D, Hansen JB, Sturis J, Markholst H. Improved beta-cell survival and reduced insulitis in a type 1 diabetic rat model after treatment with a beta-cell-selective K(ATP) channel opener. Diabetes 53: 1089-1095, 2004.
69. Song SH, Rhodes CJ, Veldhuis JD, Butler PC. Diazoxide attenuates glucose-induced defects in first-phase insulin release and pulsatile insulin secretion in human islets. Endocrinology 144: 3399-3405, 2003.
70. Spivak CE, Doyle ME. Endocannabinoid Inhibition of Ion Channels of Pancreatic Beta Cells (Abstract). Biophys J 100: 92a, 2011.
71. Standridge M, Alemzadeh R, Zemel M, Koontz J, Moustaid-Moussa N. Diazoxide down-regulates leptin and lipid metabolizing enzymes in adipose tissue of Zucker rats. FASEB J 14: 455-460, 2000.
72. Starowicz KM, Cristino L, Matias I, Capasso R, Racioppi A, Izzo AA, Di Marzo V. Endocannabinoid dysregulation in the pancreas and adipose tissue of mice fed with a high-fat diet. Obesity (Silver Spring) 16: 553-565, 2008.
73. Stephan D, Salamon E, Weber H, Russ U, Lemoine H, Quast U. KATP channel openers of the benzopyran type reach their binding site via the cytosol. Br J Pharmacol 149: 199-205, 2006.
74. Tam J, Vemuri VK, Liu J, Batkai S, Mukhopadhyay B, Godlewski G, Osei-Hyiaman D, Ohnuma S, Ambudkar SV, Pickel J, Makriyannis A, Kunos G. Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. J Clin Invest 120: 2953-2966, 2010.
75. Topol EJ, Bousser MG, Fox KA, Creager MA, Despres JP, Easton JD, Hamm CW, Montalescot G, Steg PG, Pearson TA, Cohen E, Gaudin C, Job B, Murphy JH, Bhatt DL; CRESCENDO Investigators. Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial. Lancet 376: 517-523, 2010.
76. Van Gaal L, Pi-Sunyer X, Després JP, McCarthy C, Scheen A. Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Diabetes Care 31, Suppl 2: S229-S240, 2008.
77. Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 365: 1389-1397, 2005.
78. Wajchenberg BL. Beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev 28: 187-218, 2007.
79. Yoshikawa H, Ma Z, Björklund A, Grill V. Short-term intermittent exposure to diazoxide improves functional performance of β-cells in a high-glucose environment. Am J Physiol Endocrinol Metab 287: E1202-E1208, 2004.
80. Zdravkovic M, Kruse M, Rost KL, Møss J, Kecskes A. The effects of NN414, a SUR1/Kir6.2 selective potassium channel opener in subjects with type 2 diabetes. Exp Clin Endocrinol Diabetes 115: 405-406, 2007.
81. Zdravkovic M, Kruse M, Rost KL, Møss J, Kecskes A, Dyrberg T. The effects of NN414, a SUR1/Kir6.2 selective potassium channel opener, in healthy male subjects. J Clin Pharmacol 45: 763-772, 2005.
82. Zimmer A, Zimmer AM, Hohmann AG, Herkenham M, Bonner TI. Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. Proc Natl Acad Sci USA 96: 5780-5785, 1999.