Genotype-based treatment of type 2 diabetes with an α2A-adrenergic receptor antagonist

Science Translational Medicine

Volumn 6, Issue 257, 2014, Pages

  Tang, Yunzhao ^a,b   Axelsson, Annika S ^a   Spégel, Peter ^a   Andersson, Lotta E ^a   Mulder, Hindrik ^a   Groop, Leif C ^a   Renström, Erik ^a   Rosengren, Anders H ^a  

^a LUND UNIVERSITY   (Sweden)

^b TIANJIN MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA 2 ADRENERGIC RECEPTOR; FATTY ACID; GLUCAGON; NORADRENALIN; PLACEBO; YOHIMBINE; ADRA2A PROTEIN, HUMAN; ALPHA 2 ADRENERGIC RECEPTOR BLOCKING AGENT; INSULIN;

ADULT; ALLELE; ALPHA 2 ADRENERGIC RECEPTOR GENE; ARTICLE; BLOOD PRESSURE; CLINICAL ARTICLE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE ESCALATION; FEMALE; GENE EXPRESSION; GENETIC RISK; GENETIC VARIABILITY; GENOTYPE; HUMAN; HUMAN CELL; INSULIN RELEASE; INSULIN RESPONSE; INSULIN SENSITIVITY; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; ORAL GLUCOSE TOLERANCE TEST; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME; AGED; BLOOD; DIABETES MELLITUS, TYPE 2; DRUG EFFECTS; GENETIC VARIATION; GENETICS; MIDDLE AGED; PANCREAS ISLET; PATHOPHYSIOLOGY; SECRETION (PROCESS); TRANSLATIONAL RESEARCH;

ADRENERGIC ALPHA-2 RECEPTOR ANTAGONISTS; AGED; ALLELES; BLOOD PRESSURE; DIABETES MELLITUS, TYPE 2; FATTY ACIDS, NONESTERIFIED; FEMALE; GENE EXPRESSION; GENETIC VARIATION; GENOTYPE; GLUCAGON; HUMANS; INSULIN; ISLETS OF LANGERHANS; MALE; MIDDLE AGED; NOREPINEPHRINE; RECEPTORS, ADRENERGIC, ALPHA-2; TRANSLATIONAL MEDICAL RESEARCH; YOHIMBINE;

EID: 84908374461     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3009934     Document Type: Article

References (30)

1. B. F. Voight, L. J. Scott, V. Steinthorsdottir, A. P. Morris, C. Dina, R. P. Welch, E. Zeggini, C. Huth, Y. S. Aulchenko, G. Thorleifsson, L. J. McCulloch, T. Ferreira, H. Grallert, N. Amin, G. Wu, C. J. Willer, S. Raychaudhuri, S. A. McCarroll, C. Langenberg, O. M. Hofmann, J. Dupuis, L. Qi, A. V. Segrè, M. van Hoek, P. Navarro, K. Ardlie, B. Balkau, R. Benediktsson, A. J. Bennett, R. Blagieva, E. Boerwinkle, L. L. Bonnycastle, K. Bengtsson Boström, B. Bravenboer, S. Bumpstead, N. P. Burtt, G. Charpentier, P. S. Chines, M. Cornelis, D. J. Couper, G. Crawford, A. S. Doney, K. S. Elliott, A. L. Elliott, M. R. Erdos, C. S. Fox, C. S. Franklin, M. Ganser, C. Gieger, N. Grarup, T. Green, S. Griffin, C. J. Groves, C. Guiducci, S. Hadjadj, N. Hassanali, C. Herder, B. Isomaa, A. U. Jackson, P. R. Johnson, T. Jørgensen, W. H. Kao, N. Klopp, A. Kong, P. Kraft, J. Kuusisto, T. Lauritzen, M. Li, A. Lieverse, C. M. Lindgren, V. Lyssenko, M. Marre, T. Meitinger, K. Midthjell, M. A. Morken, N. Narisu, P. Nilsson, K. R. Owen, F. Payne, J. R. Perry, A. K. Petersen, C. Platou, C. Proenc¸a, I. Prokopenko, W. Rathmann, N. W. Rayner, N. R. Robertson, G. Rocheleau, M. Roden, M. J. Sampson, R. Saxena, B. M. Shields, P. Shrader, G. Sigurdsson, T. Sparsø, K. Strassburger, H. M. Stringham, Q. Sun, A. J. Swift, B. Thorand, J. Tichet, T. Tuomi, R. M. van Dam, T. W. van Haeften, T. van Herpt, J. V. van Vliet-Ostaptchouk, G. B. Walters, M. N. Weedon, C. Wijmenga, J. Witteman, R. N. Bergman, S. Cauchi, F. S. Collins, A. L. Gloyn, U. Gyllensten, T. Hansen, W. A. Hide, G. A. Hitman, A. Hofman, D. J. Hunter, K. Hveem, M. Laakso, K. L. Mohlke, A. D. Morris, C. N. Palmer, P. P. Pramstaller, I. Rudan, E. Sijbrands, L. D. Stein, J. Tuomilehto, A. Uitterlinden, M. Walker, N. J. Wareham, R. M. Watanabe, G. R. Abecasis, B. O. Boehm, H. Campbell, M. J. Daly, A. T. Hattersley, F. B. Hu, J. B. Meigs, J. S. Pankow, O. Pedersen, H. E. Wichmann, I. Barroso, J. C. Florez, T. M. Frayling, L. Groop, R. Sladek, U. Thorsteinsdottir, J. F. Wilson, T. Illig, P. Froguel, C. M. van Duijn, K. Stefansson, D. Altshuler, M. Boehnke, M. I. McCarthy, Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat. Genet. 42, 579-589 (2010).
2. A. P. Morris, B. F. Voight, T. M. Teslovich, T. Ferreira, A. V. Segrè, V. Steinthorsdottir, R. J. Strawbridge, H. Khan, H. Grallert, A. Mahajan, I. Prokopenko, H. M. Kang, C. Dina, T. Esko, R. M. Fraser, S. Kanoni, A. Kumar, V. Lagou, C. Langenberg, J. Luan, C. M. Lindgren, M. Muller-Nurasyid, S. Pechlivanis, N. W. Rayner, L. J. Scott, S. Wiltshire, L. Yengo, L. Kinnunen, E. J. Rossin, S. Raychaudhuri, A. D. Johnson, A. S. Dimas, R. J. Loos, S. Vedantam, H. Chen, J. C. Florez, C. Fox, C. T. Liu, D. Rybin, D. J. Couper, W. H. Kao, M. Li, M. C. Cornelis, P. Kraft, Q. Sun, R. M. van Dam, H. M. Stringham, P. S. Chines, K. Fischer, P. Fontanillas, O. L. Holmen, S. E. Hunt, A. U. Jackson, A. Kong, R. Lawrence, J. Meyer, J. R. Perry, C. G. Platou, S. Potter, E. Rehnberg, N. Robertson, S. Sivapalaratnam, A. Stancakova, K. Stirrups, G. Thorleifsson, E. Tikkanen, A. R. Wood, P. Almgren, M. Atalay, R. Benediktsson, L. L. Bonnycastle, N. Burtt, J. Carey, G. Charpentier, A. T. Crenshaw, A. S. Doney, M. Dorkhan, S. Edkins, V. Emilsson, E. Eury, T. Forsen, K. Gertow, B. Gigante, G. B. Grant, C. J. Groves, C. Guiducci, C. Herder, A. B. Hreidarsson, J. Hui, A. James, A. Jonsson, W. Rathmann, N. Klopp, J. Kravic, K. Krjutskov, C. Langford, K. Leander, E. Lindholm, S. Lobbens, S. Mannisto, G. Mirza, T. W. Muhleisen, B. Musk, M. Parkin, L. Rallidis, J. Saramies, B. Sennblad, S. Shah, G. Sigurethsson, A. Silveira, G. Steinbach, B. Thorand, J. Trakalo, F. Veglia, R. Wennauer, W. Winckler, D. Zabaneh, H. Campbell, C. van Duijn, A. G. Uitterlinden, A. Hofman, E. Sijbrands, G. R. Abecasis, K. R. Owen, E. Zeggini, M. D. Trip, N. G. Forouhi, A. C. Syvanen, J. G. Eriksson, L. Peltonen, M. M. Nothen, B. Balkau, C. N. Palmer, V. Lyssenko, T. Tuomi, B. Isomaa, D. J. Hunter, L. Qi, A. R. Shuldiner, M. Roden, I. Barroso, T. Wilsgaard, J. Beilby, K. Hovingh, J. F. Price, J. F. Wilson, R. Rauramaa, T. A. Lakka, L. Lind, G. Dedoussis, I. Njolstad, N. L. Pedersen, K. T. Khaw, N. J. Wareham, S. M. Keinanen-Kiukaanniemi, T. E. Saaristo, E. Korpi-Hyovalti, J. Saltevo, M. Laakso, J. Kuusisto, A. Metspalu, F. S. Collins, K. L. Mohlke, R. N. Bergman, J. Tuomilehto, B. O. Boehm, C. Gieger, K. Hveem, S. Cauchi, P. Froguel, D. Baldassarre, E. Tremoli, S. E. Humphries, D. Saleheen, J. Danesh, E. Ingelsson, S. Ripatti, V. Salomaa, R. Erbel, K. H. Jockel, S. Moebus, A. Peters, T. Illig, U. de Faire, A. Hamsten, A. D. Morris, P. J. Donnelly, T. M. Frayling, A. T. Hattersley, E. Boerwinkle, O. Melander, S. Kathiresan, P. M. Nilsson, P. Deloukas, U. Thorsteinsdottir, L. C. Groop, K. Stefansson, F. Hu, J. S. Pankow, J. Dupuis, J. B. Meigs, D. Altshuler, M. Boehnke, M. I. McCarthy; MAGIC investigators, GIANT Consortium, Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat. Genet. 44, 981-990 (2012).
3. L. Groop, F. Pociot, Genetics of diabetes - Are we missing the genes or the disease? Mol. Cell. Endocrinol. 382, 726-739 (2014).
4. E. S. Lander, Initial impact of the sequencing of the human genome. Nature 470, 187-197 (2011).
5. K. Zhou, L. Donnelly, J. Yang, M. Li, H. Deshmukh, N. Van Zuydam, E. Ahlqvist, C. C. Spencer, L. Groop, A. D. Morris, H. M. Colhoun, P. C. Sham, M. I. McCarthy, C. N. Palmer, E. R. Pearson, Heritability of variation in glycaemic response to metformin: A genome-wide complex trait analysis. Lancet Diabetes Endocrinol. 2, 481-487 (2014).
6. J. N. Todd, J. C. Florez, An update on the pharmacogenomics of metformin: Progress, problems and potential. Pharmacogenomics 15, 529-539 (2014).
7. A. H. Rosengren, R. Jokubka, D. Tojjar, C. Granhall, O. Hansson, D. Q. Li, V. Nagaraj, T. M. Reinbothe, J. Tuncel, L. Eliasson, L. Groop, P. Rorsman, A. Salehi, V. Lyssenko, H. Luthman, E. Renström, Overexpression of alpha2A-adrenergic receptors contributes to type 2 diabetes. Science 327, 217-220 (2010).
8. X. Chen, L. Liu, W. He, Y. Lu, D. Ma, T. Du, Q. Liu, C. Chen, X. Yu, Association of the ADRA2A polymorphisms with the risk of type 2 diabetes: A meta-analysis. Clin. Biochem. 46, 722-726 (2013).
9. P. J. Talmud, J. A. Cooper, T. Gaunt, M. V. Holmes, S. Shah, J. Palmen, F. Drenos, T. Shah, M. Kumari, M. Kivimaki, J. Whittaker, D. A. Lawlor, I. N. Day, A. D. Hingorani, J. P. Casas, S. E. Humphries, Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: Meta-analysis of four prospective studies. Diabetologia 54, 1710-1719 (2011).
10. C. Liu, H. Li, L. Qi, R. J. Loos, Q. Qi, L. Lu, W. Gan, X. Lin, Variants in GLIS3 and CRY2 are associated with type 2 diabetes and impaired fasting glucose in Chinese Hans. PLOS One 6, e21464 (2011).
11. A. H. Rosengren, M. Braun, T. Mahdi, S. A. Andersson, M. E. Travers, M. Shigeto, E. Zhang, P. Almgren, C. Ladenvall, A. S. Axelsson, A. Edlund, M. G. Pedersen, A. Jonsson, R. Ramracheya, Y. Tang, J. N. Walker, A. Barrett, P. R. Johnson, V. Lyssenko, M. I. McCarthy, L. Groop, A. Salehi, A. L. Gloyn, E. Renstrom, P. Rorsman, L. Eliasson, Reduced insulin exocytosis in human pancreatic β-cells with gene variants linked to type 2 diabetes. Diabetes 61, 1726-1733 (2012).
12. J. Millstein, B. Zhang, J. Zhu, E. E. Schadt, Disentangling molecular relationships with a causal inference test. BMC Genet. 10, 23 (2009).
13. M. Dukes, Meyler's Side Effect of Drugs (Elsevier, Amsterdam, 2000), vol. 14, pp. 1024-1028.
14. J. A. Owen, S. L. Nakatsu, J. Fenemore, M. Condra, D. H. Surridge, A. Morales, The pharmacokinetics of yohimbine in man. Eur. J. Clin. Pharmacol. 32, 577-582 (1987).
15. H. Bagheri, P. Picault, L. Schmitt, G. Houin, M. Berlan, J. L. Montastruc, Pharmacokinetic study of yohimbine and its pharmacodynamic effects on salivary secretion in patients treated with tricyclic antidepressants. Br. J. Clin. Pharmacol. 37, 93-96 (1994).
16. 2A-adrenergic receptors in the genetics, pathogenesis, and treatment of type 2 diabetes. Sci. Transl. Med. 1, 12-15 (2009).
17. 2-receptor blockade. Diabetes 50, 1834-1843 (2001).
18. J. Galitzky, M. Taouis, M. Berlan, D. Rivière, M. Garrigues, M. Lafontan, Alpha 2-antagonist compounds and lipid mobilization: Evidence for a lipid mobilizing effect of oral yohimbine in healthy male volunteers. Eur. J. Clin. Invest. 18, 587-594 (1988).
19. H. Bagheri, J. J. Chale, L. N. Guyen, M. A. Tran, M. Berlan, J. L. Montastruc, Evidence for activation of both adrenergic and cholinergic nervous pathways by yohimbine, an alpha 2-adrenoceptor antagonist. Fundam. Clin. Pharmacol. 9, 248-254 (1995).
20. 2 antagonists and lipid-mobilizing strategies. Am. J. Clin. Nutr. 55, 219S-227S (1992).
21. 2-adrenergic antagonist yohimbine on orthostatic tolerance. Hypertension 15, 877-880 (1990).
22. R. F. Schäfers, J. Nürnberger, B. Herrmann, R. R. Wenzel, T. Philipp, M. C. Michel, Adrenoceptors mediating the cardiovascular and metabolic effects of α-methylnoradrenaline in humans. J. Pharmacol. Exp. Ther. 289, 918-925 (1999).
23. V. L. Broadstone, M. A. Pfeifer, V. Bajaj, J. I. Stagner, E. Samols, α-Adrenergic blockade improves glucose-potentiated insulin secretion in non-insulin-dependent diabetes mellitus. Diabetes 36, 932-937 (1987).
24. R. P. Robertson, J. B. Halter, D. Porte Jr., A role for alpha-adrenergic receptors in abnormal insulin secretion in diabetes mellitus. J. Clin. Invest. 57, 791-795 (1976).
25. 2-Adrenoceptor blockade does not enhance glucose-induced insulin release in normal subjects or patients with noninsulin-dependent diabetes. J. Clin. Endocrinol. Metab. 67, 1054-1059 (1988).
26. 2-adrenoceptor subtypes in purified rat pancreatic islet A- and B-cells. Cell. Signal. 9, 71-78 (1997).
27. F. C. Schuit, D. G. Pipeleers, Differences in adrenergic recognition by pancreatic A and B cells. Science 232, 875-877 (1986).
28. 2A-adrenergic receptor subtype. Science 273, 801-803 (1996).
29. P. Spégel, E. Ekholm, T. Tuomi, L. Groop, H. Mulder, K. Filipsson, Metabolite profiling reveals normal metabolic control in carriers of mutations in the glucokinase gene (MODY2). Diabetes 62, 653-661 (2013).
30. T. Mahdi, S. Hänzelmann, A. Salehi, S. J. Muhammed, T. M. Reinbothe, Y. Tang, A. S. Axelsson, Y. Zhou, X. Jing, P. Almgren, U. Krus, J. Taneera, A. M. Blom, V. Lyssenko, J. L. Esguerra, O. Hansson, L. Eliasson, J. Derry, E. Zhang, C. B. Wollheim, L. Groop, E. Renström, A. H. Rosengren, Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes. Cell Metab. 16, 625-633 (2012).