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http://dx.doi.org/10.4062/biomolther.2016.128

β-Adrenergic Receptor and Insulin Resistance in the Heart  

Mangmool, Supachoke (Department of Pharmacology, Faculty of Pharmacy, Mahidol University)
Denkaew, Tananat (Department of Pharmacology, Faculty of Pharmacy, Mahidol University)
Parichatikanond, Warisara (Department of Pharmacology, Faculty of Pharmacy, Mahidol University)
Kurose, Hitoshi (Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University)
Publication Information
Biomolecules & Therapeutics / v.25, no.1, 2017 , pp. 44-56 More about this Journal
Abstract
Insulin resistance is characterized by the reduced ability of insulin to stimulate tissue uptake and disposal of glucose including cardiac muscle. These conditions accelerate the progression of heart failure and increase cardiovascular morbidity and mortality in patients with cardiovascular diseases. It is noteworthy that some conditions of insulin resistance are characterized by up-regulation of the sympathetic nervous system, resulting in enhanced stimulation of ${\beta}$-adrenergic receptor (${\beta}$AR). Overstimulation of ${\beta}$ARs leads to the development of heart failure and is associated with the pathogenesis of insulin resistance in the heart. However, pathological consequences of the cross-talk between the ${\beta}$AR and the insulin sensitivity and the mechanism by which ${\beta}$AR overstimulation promotes insulin resistance remain unclear. This review article examines the hypothesis that ${\beta}$ARs overstimulation leads to induction of insulin resistance in the heart.
Keywords
${\beta}$-adrenergic receptor; ${\beta}$-blockers; G protein-coupled receptor kinase; Heart diseases; Insulin resistance; Protein kinase A;
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1 Murray, A. J., Anderson, R. E., Watson, G. C., Radda, G. K. and Clarke, K. (2004) Uncoupling proteins in human heart. Lancet 364, 1786-1788.   DOI
2 Murray, A. J., Lygate, C. A., Cole, M. A., Carr, C. A., Radda, G. K., Neubauer, S. and Clarke, K. (2006) Insulin resistance, abnormal energy metabolism and increased ischemic damage in the chronically infarcted rat heart. Cardiovasc. Res. 71, 149-157.   DOI
3 Myers, M. G., Jr., Wang, L. M., Sun, X. J., Zhang, Y., Yenush, L., Schlessinger, J., Pierce, J. H. and White, M. F. (1994) Role of IRS-1-GRB-2 complexes in insulin signaling. Mol. Cell. Biol. 14, 3577-3587.   DOI
4 Nakaya, M., Chikura, S., Watari, K., Mizuno, N., Mochinaga, K., Mangmool, S., Koyanagi, S., Ohdo, S., Sato, Y., Ide, T., Nishida, M. and Kurose, H. (2012) Induction of cardiac fibrosis by ${\beta}$-blocker in G protein-independent and G protein-coupled receptor kinase 5/${\beta}$-arrestin2-dependent signaling pathways. J. Biol. Chem. 287, 35669-35677.   DOI
5 Nichols, G. A., Gullion, C. M., Koro, C. E., Ephross, S. A. and Brown, J. B. (2004) The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care 27, 1879-1884.   DOI
6 Nikolaidis, L. A., Poornima, I., Parikh, P., Magovern, M., Shen, Y. T. and Shannon, R. P. (2006) The effects of combined versus selective adrenergic blockade on left ventricular and systemic hemodynamics, myocardial substrate preference, and regional perfusion in conscious dogs with dilated cardiomyopathy. J. Am. Coll. Cardiol. 47, 1871-1881.   DOI
7 Luan, B., Zhao, J., Wu, H., Duan, B., Shu, G., Wang, X., Li, D., Jia, W., Kang, J. and Pei, G. (2009) Deficiency of a ${\beta}$-arrestin-2 signal complex contributes to insulin resistance. Nature 457, 1146-1149.   DOI
8 Luttrell, L. M., Ferguson, S. S., Daaka, Y., Miller, W. E., Maudsley, S., Della Rocca, G. J., Lin, F., Kawakatsu, H., Owada, K., Luttrell, D. K., Caron, M. G. and Lefkowitz, R. J. (1999) ${\beta}$-arrestin-dependent formation of ${\beta}2$ adrenergic receptor-Src protein kinase complexes. Science 283, 655-661.   DOI
9 Mangmool, S., Denkaew, T., Phosri, S., Pinthong, D., Parichatikanond, W., Shimauchi, T. and Nishida, M. (2016) Sustained ${\beta}AR$ stimulation mediates cardiac insulin resistance in a PKA-dependent manner. Mol. Endocrinol. 30, 118-132.   DOI
10 Mangmool, S., Haga, T., Kobayashi, H., Kim, K. M., Nakata, H., Nishida, M. and Kurose, H. (2006) Clathrin required for phosphorylation and internalization of ${\beta}_2$-adrenergic receptor by G protein-coupled receptor kinase 2 (GRK2). J. Biol. Chem. 281, 31940-31949.   DOI
11 Mangmool, S., Shukla, A. K. and Rockman, H. A. (2010) ${\beta}$-Arrestindependent activation of $Ca^{2+}$/calmodulin kinase II after ${\beta}_1$-adrenergic receptor stimulation. J. Cell Biol. 189, 573-587.   DOI
12 Jellinger, P. S. (2007) Metabolic consequences of hyperglycemia and insulin resistance. Clin. Cornerstone 8 Suppl 7, S30-S42.
13 Nikolaidis, L. A., Sturzu, A., Stolarski, C., Elahi, D., Shen, Y. T. and Shannon, R. P. (2004) The development of myocardial insulin resistance in conscious dogs with advanced dilated cardiomyopathy. Cardiovasc. Res. 61, 297-306.   DOI
14 Nonogaki, K. (2000) New insights into sympathetic regulation of glucose and fat metabolism. Diabetologia 43, 533-549.   DOI
15 Ishibashi, K. I., Imamura, T., Sharma, P. M., Huang, J., Ugi, S. and Olefsky, J. M. (2001) Chronic endothelin-1 treatment leads to heterologous desensitization of insulin signaling in 3T3-L1 adipocytes. J. Clin. Invest. 107, 1193-1202.   DOI
16 Ishiyama-Shigemoto, S., Yamada, K., Yuan, X., Ichikawa, F. and Nonaka, K. (1999) Association of polymorphisms in the ${\beta}_2$-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus. Diabetologia 42, 98-101.   DOI
17 Izzo, R., Cipolletta, E., Ciccarelli, M., Campanile, A., Santulli, G., Palumbo, G., Vasta, A., Formisano, S., Trimarco, B. and Iaccarino, G. (2008) Enhanced GRK2 expression and desensitization of ${\beta}AR$ vasodilatation in hypertensive patients. Clin. Transl. Sci. 1, 215-220.   DOI
18 Kobayashi, H., Narita, Y., Nishida, M. and Kurose, H. (2005) ${\beta}$-arrestin2 enhances ${\beta}_2$-adrenergic receptor-mediated nuclear translocation of ERK. Cell. Signal. 17, 1248-1253.   DOI
19 Kitamura, T., Ogawa, W., Sakaue, H., Hino, Y., Kuroda, S., Takata, M., Matsumoto, M., Maeda, T., Konishi, H., Kikkawa, U. and Kasuga, M. (1998) Requirement for activation of the serine-threonine kinase Akt (protein kinase B) in insulin stimulation of protein synthesis but not of glucose transport. Mol. Cell. Biol. 18, 3708-3717.   DOI
20 Klein, J., Fasshauer, M., Ito, M., Lowell, B. B., Benito, M. and Kahn, C. R. (1999) ${\beta}_3$-adrenergic stimulation differentially inhibits insulin signaling and decreases insulin-induced glucose uptake in brown adipocytes. J. Biol. Chem. 274, 34795-34802.   DOI
21 Koch, W. J., Rockman, H. A., Samama, P., Hamilton, R. A., Bond, R. A., Milano, C. A. and Lefkowitz, R. J. (1995) Cardiac function in mice overexpressing the ${\beta}$-adrenergic receptor kinase or a ${\beta}$ ARK inhibitor. Science 268, 1350-1353.   DOI
22 Feener, E. P. and King, G. L. (1997) Vascular dysfunction in diabetes mellitus. Lancet 350 Suppl 1, SI9- SI13.
23 Marshall, J. D., Bronson, R. T., Collin, G. B., Nordstrom, A. D., Maffei, P., Paisey, R. B., Carey, C., Macdermott, S., Russell-Eggitt, I., Shea, S. E., Davis, J., Beck, S., Shatirishvili, G., Mihai, C. M., Hoeltzenbein, M., Pozzan, G. B., Hopkinson, I., Sicolo, N., Naggert, J. K. and Nishina, P. M. (2005) New Alstrom syndrome phenotypes based on the evaluation of 182 cases. Arch. Intern. Med. 165, 675-683.   DOI
24 Matthaei, S., Stumvoll, M., Kellerer, M. and Haring, H. U. (2000) Pathophysiology and pharmacological treatment of insulin resistance. Endocr. Rev. 21, 585-618.
25 Deibert, D. C. and DeFronzo, R. A. (1980) Epinephrine-induced insulin resistance in man. J. Clin. Invest. 65, 717-721.   DOI
26 Doggrell, S. A. and Henderson, C. J. (1998) The offset of ${\beta}$-adrenoceptor antagonism of the responses of the rat right ventricle to isoprenaline. J. Auton. Pharmacol. 18, 263-269.   DOI
27 Eckel, R. H., Grundy, S. M. and Zimmet, P. Z. (2005) The metabolic syndrome. Lancet 365, 1415-1428.   DOI
28 Kaestner, K. H., Flores-Riveros, J. R., McLenithan, J. C., Janicot, M. and Lane, M. D. (1991) Transcriptional repression of the mouse insulin-responsive glucose transporter (GLUT4) gene by cAMP. Proc. Natl. Acad. Sci. U.S.A. 88, 1933-1937.   DOI
29 Joost, H. G. and Steinfelder, H. J. (1987) Forskolin inhibits insulin-stimulated glucose transport in rat adipose cells by a direct interaction with the glucose transporter. Mol. Pharmacol. 31, 279-283.
30 Juhan-Vague, I., Alessi, M. C. and Vague, P. (1996) Thrombogenic and fibrinolytic factors and cardiovascular risk in non-insulin-dependent diabetes mellitus. Ann. Med. 28, 371-380.
31 Kashiwagi, A., Huecksteadt, T. P. and Foley, J. E. (1983) The regulation of glucose transport by cAMP stimulators via three different mechanisms in rat and human adipocytes. J. Biol. Chem. 258, 13685-13692.
32 Hall, R. A., Premont, R. T., Chow, C. W., Blitzer, J. T., Pitcher, J. A., Claing, A., Stoffel, R. H., Barak, L. S., Shenolikar, S., Weinman, E. J., Grinstein, S. and Lefkowitz, R. J. (1998) The ${\beta}_2$-adrenergic receptor interacts with the $Na^+$/$H^+$-exchanger regulatory factor to control $Na^+$/$H^+$ exchange. Nature 392, 626-630.   DOI
33 Kohn, A. D., Barthel, A., Kovacina, K. S., Boge, A., Wallach, B., Summers, S. A., Birnbaum, M. J., Scott, P. H., Lawrence, J. C., Jr. and Roth, R. A. (1998) Construction and characterization of a conditionally active version of the serine/threonine kinase Akt. J. Biol. Chem. 273, 11937-11943.   DOI
34 Kohn, A. D., Summers, S. A., Birnbaum, M. J. and Roth, R. A. (1996) Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. J. Biol. Chem. 271, 31372-31378.   DOI
35 Kolter, T., Uphues, I. and Eckel, J. (1997) Molecular analysis of insulin resistance in isolated ventricular cardiomyocytes of obese Zucker rats. Am. J. Physiol. 273, E59-E67.
36 Belke, D. D., Larsen, T. S., Gibbs, E. M. and Severson, D. L. (2000) Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice. Am. J. Physiol. Endocrinol. Metab. 279, E1104-E1113.   DOI
37 Bell, D. S. (2003) Heart failure: the frequent, forgotten, and often fatal complication of diabetes. Diabetes Care 26, 2433-2441.   DOI
38 Ferguson, S. S., Downey, W. E., 3rd, Colapietro, A. M., Barak, L. S., Menard, L. and Caron, M. G. (1996) Role of ${\beta}$-arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science 271, 363-366.   DOI
39 Ginsberg, H. N. (2000) Insulin resistance and cardiovascular disease. J. Clin. Invest. 106, 453-458.   DOI
40 Hayashi, K., Shibata, K., Morita, T., Iwasaki, K., Watanabe, M. and Sobue, K. (2004) Insulin receptor substrate-1/SHP-2 interaction, a phenotype-dependent switching machinery of insulin-like growth factor-I signaling in vascular smooth muscle cells. J. Biol. Chem. 279, 40807-40818.   DOI
41 Heather, L. C., Catchpole, A. F., Stuckey, D. J., Cole, M. A., Carr, C. A. and Clarke, K. (2009) Isoproterenol induces in vivo functional and metabolic abnormalities: similar to those found in the infarcted rat heart. J. Physiol. Pharmacol. 60, 31-39.
42 van Putten, J. P. and Krans, H. M. (1985) Long-term regulation of hexose uptake by isoproterenol in cultured 3T3 adipocytes. Am. J. Physiol. 248, E706-E711.
43 Usui, I., Imamura, T., Babendure, J. L., Satoh, H., Lu, J. C., Hupfeld, C. J. and Olefsky, J. M. (2005) G protein-coupled receptor kinase 2 mediates endothelin-1-induced insulin resistance via the inhibition of both Galphaq/11 and insulin receptor substrate-1 pathways in 3T3-L1 adipocytes. Mol. Endocrinol. 19, 2760-2768.   DOI
44 Usui, I., Imamura, T., Huang, J., Satoh, H., Shenoy, S. K., Lefkowitz, R. J., Hupfeld, C. J. and Olefsky, J. M. (2004a) ${\beta}$-arrestin-1 competitively inhibits insulin-induced ubiquitination and degradation of insulin receptor substrate 1. Mol. Cell. Biol. 24, 8929-8937.   DOI
45 Usui, I., Imamura, T., Satoh, H., Huang, J., Babendure, J. L., Hupfeld, C. J., and Olefsky, J. M. (2004b) GRK2 is an endogenous protein inhibitor of the insulin signaling pathway for glucose transport stimulation. EMBO J. 23, 2821-2829.   DOI
46 Wallhaus, T. R., Taylor, M., DeGrado, T. R., Russell, D. C., Stanko, P., Nickles, R. J. and Stone, C. K. (2001) Myocardial free fatty acid and glucose use after carvedilol treatment in patients with congestive heart failure. Circulation 103, 2441-2446.   DOI
47 Watson, R. T. and Pessin, J. E. (2001) Intracellular organization of insulin signaling and GLUT4 translocation. Recent Prog. Horm. Res. 56, 175-193.   DOI
48 Boden, G. and Shulman, G. I. (2002) Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and ${\beta}$-cell dysfunction. Eur. J. Clin. Invest. 32 Suppl 3, 14-23.   DOI
49 Benovic, J. L., Strasser, R. H., Caron, M. G. and Lefkowitz, R. J. (1986) ${\beta}$-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. Proc. Natl. Acad. Sci. U.S.A. 83, 2797-2801.   DOI
50 Bevan, P. (2001) Insulin signalling. J. Cell Sci. 114, 1429-1430.
51 Bos, J. L. (2006) Epac proteins: multi-purpose cAMP targets. Trends Biochem. Sci. 31, 680-686.   DOI
52 Boudina, S., Bugger, H., Sena, S., O'Neill, B. T., Zaha, V. G., Ilkun, O., Wright, J. J., Mazumder, P. K., Palfreyman, E., Tidwell, T. J., Theobald, H., Khalimonchuk, O., Wayment, B., Sheng, X., Rodnick, K. J., Centini, R., Chen, D., Litwin, S. E., Weimer, B. E. and Abel, E. D. (2009) Contribution of impaired myocardial insulin signaling to mitochondrial dysfunction and oxidative stress in the heart. Circulation 119, 1272-1283.   DOI
53 Chiasson, J. L., Shikama, H., Chu, D. T. and Exton, J. H. (1981) Inhibitory effect of epinephrine on insulin-stimulated glucose uptake by rat skeletal muscle. J. Clin. Invest. 68, 706-713.   DOI
54 Sesti, G. (2006) Pathophysiology of insulin resistance. Best Pract. Res. Clin. Endocrinol. Metab. 20, 665-679.   DOI
55 Sarbassov, D. D. and Peterson, C. A. (1998) Insulin receptor substrate-1 and phosphatidylinositol 3-kinase regulate extracellular signal-regulated kinase-dependent and -independent signaling pathways during myogenic differentiation. Mol. Endocrinol. 12, 1870-1878.   DOI
56 Sasaoka, T. and Kobayashi, M. (2000) The functional significance of Shc in insulin signaling as a substrate of the insulin receptor. Endocr. J. 47, 373-381.   DOI
57 Savage, D. B., Petersen, K. F. and Shulman, G. I. (2005) Mechanisms of insulin resistance in humans and possible links with inflammation. Hypertension 45, 828-833.   DOI
58 White, M. F. and Kahn, C. R. (1994) The insulin signaling system. J. Biol. Chem. 269, 1-4.
59 Wisler, J. W., DeWire, S. M., Whalen, E. J., Violin, J. D., Drake, M. T., Ahn, S., Shenoy, S. K. and Lefkowitz, R. J. (2007) A unique mechanism of ${\beta}$-blocker action: carvedilol stimulates ${\beta}$-arrestin signaling. Proc. Natl. Acad. Sci. U.S.A. 104, 16657-16662.   DOI
60 Scherrer, U., Randin, D., Vollenweider, P., Vollenweider, L. and Nicod, P. (1994) Nitric oxide release accounts for insulin's vascular effects in humans. J. Clin. Invest. 94, 2511-2515.   DOI
61 Shah, A. and Shannon, R. P. (2003) Insulin resistance in dilated cardiomyopathy. Rev. Cardiovasc. Med. 4 Suppl 6, S50-S57.
62 Shiina, T., Kawasaki, A., Nagao, T. and Kurose, H. (2000) Interaction with ${\beta}$-arrestin determines the difference in internalization behavior between ${\beta}1$- and ${\beta}2$-adrenergic receptors. J. Biol. Chem. 275, 29082-29090.   DOI
63 Sucharov, C. C., Mariner, P. D., Nunley, K. R., Long, C., Leinwand, L. and Bristow, M. R. (2006) A ${\beta}_1$-adrenergic receptor CaM kinase II-dependent pathway mediates cardiac myocyte fetal gene induction. Am. J. Physiol. Heart Circ. Physiol. 291, H1299-H1308.   DOI
64 Swan, J. W., Anker, S. D., Walton, C., Godsland, I. F., Clark, A. L., Leyva, F., Stevenson, J. C. and Coats, A. J. (1997) Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. J. Am. Coll. Cardiol. 30, 527-532.   DOI
65 Paolisso, G., De Riu, S., Marrazzo, G., Verza, M., Varricchio, M. and D'Onofrio, F. (1991) Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure. Metabolism 40, 972-977.   DOI
66 Oestreich, E. A., Wang, H., Malik, S., Kaproth-Joslin, K. A., Blaxall, B. C., Kelley, G. G., Dirksen, R. T. and Smrcka, A. V. (2007) Epac-mediated activation of phospholipase C(epsilon) plays a critical role in ${\beta}$-adrenergic receptor-dependent enhancement of $Ca^{2+}$ mobilization in cardiac myocytes. J. Biol. Chem. 282, 5488-5495.   DOI
67 Ohtake, T., Yokoyama, I., Watanabe, T., Momose, T., Serezawa, T., Nishikawa, J. and Sasaki, Y. (1995) Myocardial glucose metabolism in noninsulin-dependent diabetes mellitus patients evaluated by FDG-PET. J. Nucl. Med. 36, 456-463.
68 Olefsky, J., Farquhar, J. W. and Reaven, G. (1973) Relationship between fasting plasma insulin level and resistance to insulin-mediated glucose uptake in normal and diabetic subjects. Diabetes 22, 507-513.   DOI
69 McFarlane, S. I., Banerji, M. and Sowers, J. R. (2001) Insulin resistance and cardiovascular disease. J. Clin. Endocrinol. Metab. 86, 713-718.
70 Mazumder, P. K., O'Neill, B. T., Roberts, M. W., Buchanan, J., Yun, U. J., Cooksey, R. C., Boudina, S. and Abel, E. D. (2004) Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes 53, 2366-2374.   DOI
71 Mingrone, G., DeGaetano, A., Greco, A. V., Capristo, E., Benedetti, G., Castagneto, M. and Gasbarrini, G. (1997) Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids. Diabetologia 40, 599-605.   DOI
72 Morisco, C., Lembo, G. and Trimarco, B. (2006) Insulin resistance and cardiovascular risk: New insights from molecular and cellular biology. Trends Cardiovasc. Med. 16, 183-188.   DOI
73 Paolisso, G., Manzella, D., Rizzo, M. R., Ragno, E., Barbieri, M., Varricchio, G. and Varricchio, M. (2000) Elevated plasma fatty acid concentrations stimulate the cardiac autonomic nervous system in healthy subjects. Am. J. Clin. Nutr. 72, 723-730.   DOI
74 Park, S. Y., Cho, Y. R., Kim, H. J., Higashimori, T., Danton, C., Lee, M. K., Dey, A., Rothermel, B., Kim, Y. B., Kalinowski, A., Russell, K. S. and Kim, J. K. (2005) Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice. Diabetes 54, 3530-3540.   DOI
75 Paternostro, G., Camici, P. G., Lammerstma, A. A., Marinho, N., Baliga, R. R., Kooner, J. S., Radda, G. K. and Ferrannini, E. (1996) Cardiac and skeletal muscle insulin resistance in patients with coronary heart disease. A study with positron emission tomography. J. Clin. Invest. 98, 2094-2099.   DOI
76 Kotani, K., Ogawa, W., Matsumoto, M., Kitamura, T., Sakaue, H., Hino, Y., Miyake, K., Sano, W., Akimoto, K., Ohno, S. and Kasuga, M. (1998) Requirement of atypical protein kinase clambda for insulin stimulation of glucose uptake but not for Akt activation in 3T3-L1 adipocytes. Mol. Cell. Biol. 18, 6971-6982.   DOI
77 Krupnick, J. G. and Benovic, J. L. (1998) The role of receptor kinases and arrestins in G protein-coupled receptor regulation. Annu. Rev. Pharmacol. Toxicol. 38, 289-319.   DOI
78 Montagnani, M., Ravichandran, L. V., Chen, H., Esposito, D. L. and Quon, M. J. (2002) Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells. Mol. Endocrinol. 16, 1931-1942.   DOI
79 Morisco, C., Condorelli, G., Trimarco, V., Bellis, A., Marrone, C., Condorelli, G., Sadoshima, J. and Trimarco, B. (2005) Akt mediates the cross-talk between ${\beta}$-adrenergic and insulin receptors in neonatal cardiomyocytes. Circ. Res. 96, 180-188.   DOI
80 Morisco, C., Marrone, C., Trimarco, V., Crispo, S., Monti, M. G., Sadoshima, J. and Trimarco, B. (2007) Insulin resistance affects the cytoprotective effect of insulin in cardiomyocytes through an impairment of MAPK phosphatase-1 expression. Cardiovasc. Res. 76, 453-464.   DOI
81 Mulder, A. H., Tack, C. J., Olthaar, A. J., Smits, P., Sweep, F. C. and Bosch, R. R. (2005) Adrenergic receptor stimulation attenuates insulin-stimulated glucose uptake in 3T3-L1 adipocytes by inhibiting GLUT4 translocation. Am. J. Physiol. Endocrinol. Metab. 289, E627-E633.   DOI
82 Lee, A. D., Hansen, P. A., Schluter, J., Gulve, E. A., Gao, J. and Holloszy, J. O. (1997) Effects of epinephrine on insulin-stimulated glucose uptake and GLUT-4 phosphorylation in muscle. Am. J. Physiol. 273, C1082-C1087.   DOI
83 Kuboki, K., Jiang, Z. Y., Takahara, N., Ha, S. W., Igarashi, M., Yamauchi, T., Feener, E. P., Herbert, T. P., Rhodes, C. J. and King, G. L. (2000) Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo : a specific vascular action of insulin. Circulation 101, 676-681.   DOI
84 Lager, I. (1991) The insulin-antagonistic effect of the counterregulatory hormones. J. Intern. Med. Suppl. 735, 41-47.
85 Lamounier-Zepter, V., Ehrhart-Bornstein, M. and Bornstein, S. R. (2006) Insulin resistance in hypertension and cardiovascular disease. Best Pract. Res. Clin. Endocrinol. Metab. 20, 355-367.   DOI
86 Lee, J. and Pilch, P. F. (1994) The insulin receptor: structure, function, and signaling. Am. J. Physiol. 266, C319-C334.   DOI
87 Lefkowitz, R. J., Rajagopal, K. and Whalen, E. J. (2006) New roles for ${\beta}$-arrestins in cell signaling: not just for seven-transmembrane receptors. Mol. Cell 24, 643-652.   DOI
88 Lefkowitz, R. J. and Shenoy, S. K. (2005) Transduction of receptor signals by ${\beta}$-arrestins. Science 308, 512-517.   DOI
89 Hillier, T. A. and Pedula, K. L. (2003) Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care 26, 2999-3005.   DOI
90 Heck, P. M. and Dutka, D. P. (2009) Insulin resistance and heart failure. Curr. Heart Fail. Rep. 6, 89-94.   DOI
91 Hoffmann, C., Leitz, M. R., Oberdorf-Maass, S., Lohse, M. J. and Klotz, K. N. (2004) Comparative pharmacology of human ${\beta}$-adrenergic receptor subtypes-characterization of stably transfected receptors in CHO cells. Naunyn Schmiedebergs Arch. Pharmacol. 369, 151-159.
92 How, O. J., Aasum, E., Severson, D. L., Chan, W. Y., Essop, M. F. and Larsen, T. S. (2006) Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice. Diabetes 55, 466-473.   DOI
93 Hu, L. A., Tang, Y., Miller, W. E., Cong, M., Lau, A. G., Lefkowitz, R. J. and Hall, R. A. (2000) ${\beta}_1$-adrenergic receptor association with PSD-95. Inhibition of receptor internalization and facilitation of ${\beta}_1$-adrenergic receptor interaction with N-methyl-D-aspartate receptors. J. Biol. Chem. 275, 38659-38666.   DOI
94 Iaccarino, G., Barbato, E., Cipolleta, E., Esposito, A., Fiorillo, A., Koch, W. J. and Trimarco, B. (2001) Cardiac ${\beta}ARK1$ upregulation induced by chronic salt deprivation in rats. Hypertension 38, 255-260.   DOI
95 Coats, A. J. and Anker, S. D. (2000) Insulin resistance in chronic heart failure. J. Cardiovasc. Pharmacol. 35, S9-S14.   DOI
96 Akhter, S. A., Luttrell, L. M., Rockman, H. A., Iaccarino, G., Lefkowitz, R. J. and Koch, W. J. (1998) Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy. Science 280, 574-577.   DOI
97 Akikawa, R., Nawano, M., Gu, Y., Katagiri, H., Asano, T., Zhu, W., Nagai, R. and Komuro, I. (2000) Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 kinase/Akt. Circulation 102, 2873-2879.   DOI
98 Chirieac, D. V., Chirieac, L. R., Corsetti, J. P., Cianci, J., Sparks, C. E. and Sparks, J. D. (2000) Glucose-stimulated insulin secretion suppresses hepatic triglyceride-rich lipoprotein and apoB production. Am. J. Physiol. Endocrinol. Metab. 279, E1003-E1011.   DOI
99 Ciccarelli, M., Chuprun, J. K., Rengo, G., Gao, E., Wei, Z., Peroutka, R. J., Gold, J. I., Gumpert, A., Chen, M., Otis, N. J., Dorn, G. W., 2nd, Trimarco, B., Iaccarino, G. and Koch, W. J. (2011) G proteincoupled receptor kinase 2 activity impairs cardiac glucose uptake and promotes insulin resistance after myocardial ischemia. Circulation 123, 1953-1962.   DOI
100 Cipolletta, E., Campanile, A., Santulli, G., Sanzari, E., Leosco, D., Campiglia, P., Trimarco, B. and Iaccarino, G. (2009) The G protein coupled receptor kinase 2 plays an essential role in ${\beta}$-adrenergic receptor-induced insulin resistance. Cardiovasc. Res. 84, 407-415.   DOI
101 Communal, C., Singh, K., Sawyer, D. B. and Colucci, W. S. (1999) Opposing effects of ${\beta}_1$- and ${\beta}_2$-adrenergic receptors on cardiac myocyte apoptosis : role of a pertussis toxin-sensitive G protein. Circulation 100, 2210-2212.   DOI
102 Beaulieu, J. M., Sotnikova, T. D., Marion, S., Lefkowitz, R. J., Gainetdinov, R. R. and Caron, M. G. (2005) An Akt/${\beta}$-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell 122, 261-273.   DOI
103 Iaccarino, G., Barbato, E., Cipolletta, E., De Amicis, V., Margulies, K. B., Leosco, D., Trimarco, B. and Koch, W. J. (2005a) Elevated myocardial and lymphocyte GRK2 expression and activity in human heart failure. Eur. Heart J. 26, 1752-1758.   DOI
104 Iaccarino, G., Trimarco, V., Lanni, F., Cipolletta, E., Izzo, R., Arcucci, O., De Luca, N. and Di Renzo, G. (2005b) ${\beta}$-Blockade and increased dyslipidemia in patients bearing Glu27 variant of ${\beta}_2$ adrenergic receptor gene. Pharmacogenomics J. 5, 292-297.   DOI
105 Anis, Y., Leshem, O., Reuveni, H., Wexler, I., Ben Sasson, R., Yahalom, B., Laster, M., Raz, I., Ben Sasson, S., Shafrir, E. and Ziv, E. (2004) Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes. Diabetologia 47, 1232-1244.   DOI
106 Backer, J. M., Myers, M. G., Jr., Shoelson, S. E., Chin, D. J., Sun, X. J., Miralpeix, M., Hu, P., Margolis, B., Skolnik, E. Y. and Schlessinger, J. (1992) Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during insulin stimulation. EMBO J. 11, 3469-3479.
107 Bangalore, S., Messerli, F. H., Kostis, J. B. and Pepine, C. J. (2007) Cardiovascular protection using ${\beta}$-blockers: a critical review of the evidence. J. Am. Coll. Cardiol. 50, 563-572.   DOI
108 Becker, A. B. and Roth, R. A. (1990) Insulin receptor structure and function in normal and pathological conditions. Annu. Rev. Med. 41, 99-115.   DOI
109 Witteles, R. M. and Fowler, M. B. (2008) Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options. J. Am. Coll. Cardiol. 51, 93-102.   DOI
110 Yamada, K., Ishiyama-Shigemoto, S., Ichikawa, F., Yuan, X., Koyanagi, A., Koyama, W. and Nonaka, K. (1999) Polymorphism in the 5'-leader cistron of the ${\beta}_2$-adrenergic receptor gene associated with obesity and type 2 diabetes. J. Clin. Endocrinol. Metab. 84, 1754-1757.
111 DeFronzo, R. A. and Tripathy, D. (2009) Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 32 Suppl 2, S157-S163.   DOI
112 Czech, M. P. and Corvera, S. (1999) Signaling mechanisms that regulate glucose transport. J. Biol. Chem. 274, 1865-1868.   DOI
113 De Meyts, P. (2004) Insulin and its receptor: structure, function and evolution. Bioessays 26, 1351-1362.   DOI
114 DeFronzo, R. A. (2004) Pathogenesis of type 2 diabetes mellitus. Med. Clin. North Am. 88, 787-835.   DOI
115 Thomas, J. A. and Marks, B. H. (1978) Plasma norepinephrine in congestive heart failure. Am. J. Cardiol. 41, 233-243.   DOI
116 Swan, J. W., Walton, C., Godsland, I. F., Clark, A. L., Coats, A. J. and Oliver, M. F. (1994) Insulin resistance in chronic heart failure. Eur. Heart J. 15, 1528-1532.   DOI
117 Taguchi, K., Matsumoto, T., Kamata, K. and Kobayashi, T. (2012) G protein-coupled receptor kinase 2, with ${\beta}$-arrestin 2, impairs insulin-induced Akt/endothelial nitric oxide synthase signaling in ob/ob mouse aorta. Diabetes 61, 1978-1985.   DOI
118 Taniguchi, C. M., Emanuelli, B. and Kahn, C. R. (2006) Critical nodes in signalling pathways: insights into insulin action. Nat. Rev. Mol. Cell Biol. 7, 85-96.
119 Trovati, M. and Anfossi, G. (1998) Insulin, insulin resistance and platelet function: similarities with insulin effects on cultured vascular smooth muscle cells. Diabetologia 41, 609-622.   DOI
120 Ullrich, A., Bell, J. R., Chen, E. Y., Herrera, R., Petruzzelli, L. M., Dull, T. J., Gray, A., Coussens, L., Liao, Y. C., Tsubokawa, M., Mason, P. H., Seeburg, C., Grunfeld, O., Rosen, M. and Ramachandran, J. (1985) Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 313, 756-761.   DOI
121 Ungerer, M., Bohm, M., Elce, J. S., Erdmann, E. and Lohse, M. J. (1993) Altered expression of ${\beta}$-adrenergic receptor kinase and ${\beta}1$-adrenergic receptors in the failing human heart. Circulation 87, 454-463.   DOI
122 Zhu, W. Z., Wang, S. Q., Chakir, K., Yang, D., Zhang, T., Brown, J. H., Devic, E., Kobilka, B. K., Cheng, H. and Xiao, R. P. (2003) Linkage of ${\beta}_1$-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of $Ca^{2+}$/calmodulin kinase II. J. Clin. Invest. 111, 617-625.   DOI
123 Yoo, B., Lemaire, A., Mangmool, S., Wolf, M. J., Curcio, A., Mao, L. and Rockman, H. A. (2009) ${\beta}_1$-adrenergic receptors stimulate cardiac contractility and CaMKII activation in vivo and enhance cardiac dysfunction following myocardial infarction. Am. J. Physiol. Heart Circ. Physiol. 297, H1377-H1386.   DOI
124 Yu, Q., Gao, F. and Ma, X. L. (2011) Insulin says NO to cardiovascular disease. Cardiovasc. Res. 89, 516-524.   DOI
125 Zhao, F. Q. and Keating, A. F. (2007) Functional properties and genomics of glucose transporters. Curr. Genomics 8, 113-128.   DOI
126 Penn, R. B., Pronin, A. N. and Benovic, J. L. (2000) Regulation of G protein-coupled receptor kinases. Trends Cardiovasc. Med. 10, 81-89.   DOI
127 Paternostro, G., Clarke, K., Heath, J., Seymour, A. M. and Radda, G. K. (1995) Decreased GLUT-4 mRNA content and insulin-sensitive deoxyglucose uptake show insulin resistance in the hypertensive rat heart. Cardiovasc. Res. 30, 205-211.   DOI
128 Ungerer, M., Parruti, G., Bohm, M., Puzicha, M., DeBlasi, A., Erdmann, E. and Lohse, M. J. (1994) Expression of ${\beta}$-arrestins and ${\beta}$-adrenergic receptor kinases in the failing human heart. Circ. Res. 74, 206-213.   DOI
129 Paternostro, G., Pagano, D., Gnecchi-Ruscone, T., Bonser, R. S. and Camici, P. G. (1999) Insulin resistance in patients with cardiac hypertrophy. Cardiovasc. Res. 42, 246-253.   DOI
130 Penela, P., Ribas, C. and Mayor, F., Jr. (2003) Mechanisms of regulation of the expression and function of G protein-coupled receptor kinases. Cell. Signal. 15, 973-981.   DOI
131 Pierce, K. L., Premont, R. T. and Lefkowitz, R. J. (2002) Seven-transmembrane receptors. Nat. Rev. Mol. Cell Biol. 3, 639-650.   DOI
132 Postic, C., Leturque, A., Rencurel, F., Printz, R. L., Forest, C., Granner, D. K. and Girard, J. (1993) The effects of hyperinsulinemia and hyperglycemia on GLUT4 and hexokinase II mRNA and protein in rat skeletal muscle and adipose tissue. Diabetes 42, 922-929.   DOI
133 Randle, P. J., Garland, P. B., Hales, C. N. and Newsholme, E. A. (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1, 785-789.
134 Reaven, G. M. (1991) Insulin resistance, hyperinsulinemia, and hypertriglyceridemia in the etiology and clinical course of hypertension. Am. J. Med. 90, 7S-12S.   DOI
135 Rockman, H. A., Koch, W. J. and Lefkowitz, R. J. (2002) Seven-transmembrane-spanning receptors and heart function. Nature 415, 206-212.   DOI
136 Salazar, N. C., Chen, J. and Rockman, H. A. (2007) Cardiac GPCRs: GPCR signaling in healthy and failing hearts. Biochim. Biophys. Acta 1768, 1006-1018.   DOI