Diabetes mellitus (DM) induces a large number of diseases of the nervous, cardiovascular, and some other systems of the organism. One of the main causes of the diseases is the changes in the functional activity of hormonal signaling systems which lead to the alterations and abnormalities of the cellular processes and contribute to triggering and developing many DM complications. The key role in the control of physiological and biochemical processes belongs to the adenylyl cyclase (AC) signaling system, sensitive to biogenic amines and polypeptide hormones. The review is devoted to the changes in the GPCR-G protein-AC system in the brain, heart, skeletal muscles, liver, and the adipose tissue in experimental and human DM of the types 1 and 2 and also to the role of the changes in AC signaling in the pathogenesis and etiology of DM and its complications. It is shown that the changes of the functional state of hormone-sensitive AC system are dependent to a large extent on the type and duration of DM and in experimental DM on the model of the disease. The degree of alterations and abnormalities of AC signaling pathways correlates very well with the severity of DM and its complications. 1. Introduction Diabetes mellitus (DM) is a major global health problem affecting, according to the World Health Organization, more than 346 million people worldwide [1]. It is one of the most severe metabolic disorders in humans characterized by hyperglycemia due to a relative or an absolute deficiency of insulin or the resistance of target tissue to regulatory action of the hormone, or both. Type 1, insulin-dependent and type 2, non-insulin-dependent DM (T1DM1 and T2DM2) both induce a large number of diseases and dysfunctions of the nervous, cardiovascular, excretory, reproductive, and other systems of the organism [2–9]. Severe complications of DM are found in more than a quarter of diabetic patients. A new view of the nature and pathogenesis of DM-induced complications shared by many specialists nowadays has been prompted by the study of functional activity of hormonal signaling systems regulated by insulin, insulin-like growth factor-1 (IGF-1), and leptin, the principal players responsible for the development of DM and its central and peripheral complications, and by a wide spectrum of other hormones and neurotransmitters, including biogenic amines, purines, glutamate, peptide, and glycoprotein hormones controlling the fundamental cellular processes. The data were obtained showing that the alterations and abnormalities of functional activity of these systems and the
References
[1]
S. R. Shrivastava, P. S. Shrivastava, and J. Ramasamy, “Role of self-care in management of diabetes mellitus,” Journal of Diabetes and Metabolic Disorders, vol. 12, no. 1, article 14, 2013.
[2]
M. C. Stiles and E. R. Seaquist, “Cerebral structural and functional changes in type 1 diabetes,” Minerva Medica, vol. 101, no. 2, pp. 105–114, 2010.
[3]
C. E. Tabit, W. B. Chung, N. M. Hamburg, and J. A. Vita, “Endothelial dysfunction in diabetes mellitus: molecular mechanisms and clinical implications,” Reviews in Endocrine & Metabolic Disorders, vol. 11, pp. 61–74, 2010.
[4]
S. E. Nelson, “Management of patients with type 2 diabetes,” Current Medical Research and Opinion, vol. 27, pp. 1931–1947, 2011.
[5]
M. Chiha, M. Njeim, and E. G. Chedrawy, “Diabetes and coronary heart disease: a risk factor for the global epidemic,” International Journal of Hypertension, vol. 2012, Article ID 697240, 7 pages, 2012.
[6]
M. Louraki, C. Karayianni, C. Kanaka-Gantenbein, M. Katsalouli, and K. Karavanaki, “Peripheral neuropathy in children with type 1 diabetes,” Diabetes and Metabolism, vol. 38, no. 4, pp. 281–289, 2012.
[7]
S. N. Magge, “Cardiovascular risk in children and adolescents with type 1 and type 2 diabetes mellitus,” Current Cardiovascular Risk Reports, vol. 6, no. 6, pp. 591–600, 2012.
[8]
B. N. Mercer, S. Morais, R. M. Cubbon, and M. T. Kearney, “Diabetes mellitus and the heart,” International Journal of Clinical Practice, vol. 66, no. 7, pp. 640–647, 2012.
[9]
H. Umegaki, T. Hayashi, H. Nomura et al., “Cognitive dysfunction: an emerging concept of a new diabetic complication in the elderly,” Geriatrics and Gerontology International, vol. 13, no. 1, pp. 28–34, 2013.
[10]
V. M. Altan, E. Arioglu, S. Guner, and A. T. Ozcelikay, “The influence of diabetes on cardiac β-adrenoceptor subtypes,” Heart Failure Reviews, vol. 12, no. 1, pp. 58–65, 2007.
[11]
T. H. Meek and G. J. Morton, “Leptin, diabetes, and the brain,” Indian Journal of Endocrinology and Metabolism, vol. 16, supplement 3, pp. 534–542, 2012.
[12]
A. O. Shpakov, “Alterations in hormonal signaling systems in diabetes mellitus: origin, causality and specificity,” Endocrinology and Metabolic Syndrome, vol. 1, article e106, 2012.
[13]
A. O. Shpakov, “The functional state of biogenic amines- and acetylcholine-regulated signaling systems of the brain in diabetes mellitus,” Tsitologiia, vol. 54, no. 6, pp. 459–468, 2012.
[14]
A. O. Shpakov and K. V. Derkach, “The brain peptidergic signaling systems in diabetes mellitus,” Tsitologiia, vol. 54, no. 10, pp. 733–741, 2012.
[15]
K. Soumaya, “Molecular mechanisms of insulin resistance in diabetes,” Advances in Experimental Medicine and Biology, vol. 771, pp. 240–251, 2012.
[16]
G.-J. Biessels, A. Kamal, G. M. Ramakers et al., “Place learning and hippocampal synaptic plasticity in streptozotocin-induced diabetic rats,” Diabetes, vol. 45, no. 9, pp. 1259–1266, 1996.
[17]
A. J. Scheen, “Central nervous system: a conductor orchestrating metabolic regulations harmed by both hyperglycaemia and hypoglycaemia,” Diabetes and Metabolism, vol. 36, no. 3, pp. S31–S38, 2010.
[18]
J. Jackson and C. S. Paulose, “Enhancement of [m-methoxy 3H]MDL100907 binding to 5HT(2A) receptors in cerebral cortex and brain stem of streptozotocin induced diabetic rats,” Molecular and Cellular Biochemistry, vol. 199, no. 1-2, pp. 81–85, 1999.
[19]
G. Gireesh, S. Balarama Kaimal, T. Peeyush Kumar, and C. S. Paulose, “Decreased muscarinic M1 receptor gene expression in the hypothalamus, brainstem, and pancreatic islets of streptozotocin-induced diabetic rats,” Journal of Neuroscience Research, vol. 86, no. 4, pp. 947–953, 2008.
[20]
S. Antony, T. Peeyush Kumar, J. Mathew, T. R. Anju, and C. S. Paulose, “Hypoglycemia induced changes in cholinergic receptor expression in the cerebellum of diabetic rats,” Journal of Biomedical Science, vol. 17, no. 1, article 7, 2010.
[21]
J. Anu, T. Peeyush Kumar, M. S. Nandhu, and C. S. Paulose, “Enhanced NMDAr1, NMDA2b and mGlu5 receptors gene expression in the cerebellum of insulin induced hypoglycaemic and streptozotocin induced diabetic rats,” European Journal of Pharmacology, vol. 630, no. 1–3, pp. 61–68, 2010.
[22]
T. P. Kumar, S. Antony, G. Gireesh, N. George, and C. S. Paulose, “Curcumin modulates dopaminergic receptor, CREB and phospholipase C gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats,” Journal of Biomedical Science, vol. 17, p. 43, 2010.
[23]
A. Shpakov, O. Chistyakova, K. Derkach, and V. Bondareva, “Hormonal signaling systems of the brain in diabetes mellitus,” in Neurodegenerative Diseases, R. C. Chang, Ed., pp. 349–386, Intech Open Access Publisher, Rijeka, Croatia, 2011.
[24]
M. Seed Ahmed, A. Kovoor, S. Nordman et al., “Increased expression of adenylyl cyclase 3 in pancreatic islets and central nervous system of diabetic Goto-Kakizaki rats: a possible regulatory role in glucose homeostasis,” Islets, vol. 4, no. 5, pp. 343–348, 2012.
[25]
A. Sherin, J. Anu, K. T. Peeyush et al., “Cholinergic and GABAergic receptor functional deficit in the hippocampus of insulin-induced hypoglycemic and streptozotocin-induced diabetic rats,” Neuroscience, vol. 202, pp. 69–76, 2012.
[26]
S. Jayanarayanan, S. Smijin, K. T. Peeyush, T. R. Anju, and C. S. Paulose, “NMDA and AMPA receptor mediated excitotoxicity in cerebral cortex of streptozotocin induced diabetic rat: ameliorating effects of curcumin,” Chemico-Biological Interactions, vol. 201, no. 1–3, pp. 39–48, 2013.
[27]
H. Pijl and E. A. Meinders, “Modulation of monoaminergic neural circuits: potential for the treatment of type 2 diabetes mellitus,” Treatments in Endocrinology, vol. 1, no. 2, pp. 71–78, 2002.
[28]
P. N. E. Shankar, A. Joseph, and C. S. Paulose, “Decreased [3H] YM-09151-2 binding to dopamine D2 receptors in the hypothalamus, brainstem and pancreatic islets of streptozotocin-induced diabetic rats,” European Journal of Pharmacology, vol. 557, no. 2-3, pp. 99–105, 2007.
[29]
M. Anitha, P. M. Abraham, and C. S. Paulose, “Striatal dopamine receptors modulate the expression of insulin receptor, IGF-1 and GLUT-3 in diabetic rats: effect of pyridoxine treatment,” European Journal of Pharmacology, vol. 696, no. 1–3, pp. 54–61, 2012.
[30]
S. Finkbeiner, “CREB couples neurotrophin signals to survival messages,” Neuron, vol. 25, no. 1, pp. 11–14, 2000.
[31]
A. O. Shpakov, L. A. Kuznetsova, S. A. Plesneva, and M. N. Pertseva, “Molecular mechanisms of modified sensitivity of the adenylate cyclase signaling system to biogenic amines during streptozotocin-induced diabetes,” Bulletin of Experimental Biology and Medicine, vol. 140, no. 3, pp. 304–308, 2005.
[32]
A. Shpakov, K. Derkach, I. Moyseyuk, and O. Chistyakova, “Alterations of hormone-sensitive adenylyl cyclase system in the tissues of rats with long-term streptozotocin diabetes and the influence of intranasal insulin,” Dataset Papers in Pharmacology, vol. 2013, Article ID 698435, 14 pages, 2013.
[33]
A. O. Shpakov, O. V. Chistyakova, K. V. Derkach, I. V. Moyseyuk, and V. M. Bondareva, “Intranasal insulin affects adenyl cyclase system in rat tissues in neonatal diabetes,” Central European Journal of Biology, vol. 7, no. 1, pp. 33–47, 2012.
[34]
A. O. Shpakov, L. A. Kuznetsova, S. A. Plesneva et al., “Decrease in functional activity of G-proteins hormone-sensitive adenylate cyclase signaling system, during experimental type II diabetes mellitus,” Bulletin of Experimental Biology and Medicine, vol. 142, no. 6, pp. 685–689, 2006.
[35]
A. O. Shpakov, K. V. Derkach, O. V. Chistyakova, I. B. Sukhov, V. N. Shipilov, and V. M. Bondareva, “The brain adenylyl cyclase signaling system and cognitive functions in rat with neonatal diabetes under the influence of intranasal serotonin,” Journal of Metabolic Syndrome, vol. 1, no. 2, Article ID 1000104, 2012.
[36]
A. O. Shpakov, L. A. Kuznetsova, S. A. Plesneva, I. A. Gur'ianov, G. P. Vlasov, and M. N. Pertseva, “Identifications of disturbances in hormone-sensitive adenylyl cyclase system in the tissues of rats with types 1 and 2 diabetes using functional probes and synthetic peptides,” Tekhnologii Zhivykh System, vol. 4, pp. 96–108, 2007.
[37]
D. Y. Kuo, “Hypothalamic neuropeptide Y (NPY) and the attenuation of hyperphagia in streptozotocin diabetic rats treated with dopamine D1/D2 agonists,” British Journal of Pharmacology, vol. 148, no. 5, pp. 640–647, 2006.
[38]
I. Papazoglou, F. Berthou, N. Vicaire et al., “Hypothalamic serotonin-insulin signaling cross-talk and alterations in a type 2 diabetic model,” Molecular and Cellular Endocrinology, vol. 350, no. 1, pp. 136–144, 2012.
[39]
S. Haider, S. Ahmed, S. Tabassum, Z. Memon, M. Ikram, and D. J. Haleem, “Streptozotocin-induced insulin deficiency leads to development of behavioral deficits in rats,” Acta Neurologica Belgica, vol. 113, no. 1, pp. 35–41, 2013.
[40]
J. X. Li and C. P. France, “Food restriction and streptozotocin treatment decrease 5-HT1A and 5-HT2A receptor-mediated behavioral effects in rats,” Behavioural Pharmacology, vol. 19, no. 4, pp. 292–297, 2008.
[41]
A. O. Shpakov, K. V. Derkach, I. V. Moyseyuk, O. V. Chistyakova, and V. M. Bondareva, “Hormonal sensitivity of adenylyl cyclase in the myocardium, brain and testes of 18-month-old non-diabetic and diabetic rats,” International Journal of Biochemistry Research & Review, vol. 3, no. 1, pp. 1–20, 2013.
[42]
K. Tully and V. Y. Bolshakov, “Emotional enhancement of memory: how norepinephrine enables synaptic plasticity,” Molecular Brain, vol. 3, p. 15, 2010.
[43]
D. R. Garris, “Age-and diabetes-associated alterations in regional brain norepinephrine concentrations and adrenergic receptor populations in C57BL/KsJ mice,” Developmental Brain Research, vol. 51, no. 2, pp. 161–166, 1990.
[44]
P. S. Padayatti and C. S. Paulose, “α2 adrenergic and high affinity serotonergic receptor changes in the brain stem of streptozotocin-induced diabetic rats,” Life Sciences, vol. 65, no. 4, pp. 403–414, 1999.
[45]
M. S. Bitar and E. B. DeSouza, “Diabetes-related changes in brain beta adrenoreceptors in rats as assessed by quantitative autoradiography: relationship to hypothalamic norepinephrine metabolism and pituitary-gonadal hormone secretion,” The Journal of Pharmacology and Experimental Therapeutics, vol. 254, no. 3, pp. 781–785, 1990.
[46]
M. S. Magnoni, H. Kobayashi, and E. Trezzi, “β-adrenergic receptors in brain microvessels of diabetic rats,” Life Sciences, vol. 34, no. 11, pp. 1095–1100, 1984.
[47]
A. D. Mooradian and P. J. Scarpace, “β-adrenergic receptor activity of cerebral microvessels in experimental diabetes mellitus,” Brain Research, vol. 583, no. 1-2, pp. 155–160, 1992.
[48]
I. S. Farooqi, J. M. Keogh, G. S. H. Yeo, E. J. Lank, T. Cheetham, and S. O'Rahilly, “Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene,” The New England Journal of Medicine, vol. 348, no. 12, pp. 1085–1095, 2003.
[49]
N. Balthasar, L. T. Dalgaard, C. E. Lee et al., “Divergence of melanocortin pathways in the control of food intake and energy expenditure,” Cell, vol. 123, no. 3, pp. 493–505, 2005.
[50]
W. Fan, D. M. Dinulescu, A. A. Butler, J. Zhou, D. L. Marks, and R. D. Cone, “The central melanocortin system can directly regulate serum insulin levels,” Endocrinology, vol. 141, no. 9, pp. 3072–3079, 2000.
[51]
S. Obici, Z. Feng, J. Tan, L. Liu, G. Karkanias, and L. Rossetti, “Central melanocortin receptors regulate insulin action,” The Journal of Clinical Investigation, vol. 108, no. 7, pp. 1079–1085, 2001.
[52]
R. Nogueiras, P. Wiedmer, D. Perez-Tilve et al., “The central melanocortin system directly controls peripheral lipid metabolism,” The Journal of Clinical Investigation, vol. 117, no. 11, pp. 3475–3488, 2007.
[53]
C. Haskell-Luevano, J. W. Schaub, A. Andreasen et al., “Voluntary exercise prevents the obese and diabetic metabolic syndrome of the melanocortin-4 receptor knockout mouse,” FASEB Journal, vol. 23, no. 2, pp. 642–655, 2009.
[54]
P. J. Havel, T. M. Hahn, D. K. Sindelar et al., “Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats,” Diabetes, vol. 49, no. 2, pp. 244–252, 2000.
[55]
J. Gout, D. Sarafian, J. Tirard et al., “Leptin infusion and obesity in mouse cause alterations in the hypothalamic melanocortin system,” Obesity, vol. 16, no. 8, pp. 1763–1769, 2008.
[56]
D. Giuliani, C. Mioni, D. Altavilla et al., “Both early and delayed treatment with melanocortin 4 receptor-stimulating melanocortins produces neuroprotection in cerebral ischemia,” Endocrinology, vol. 147, no. 3, pp. 1126–1135, 2006.
[57]
J. B. Tatro, “Melanocortins defend their territory: multifaceted neuroprotection in cerebral ischemia,” Endocrinology, vol. 147, no. 3, pp. 1122–1125, 2006.
[58]
R. P. Nargund, A. M. Strack, and T. M. Fong, “Melanocortin-4 receptor (MC4R) agonists for the treatment of obesity,” Journal of Medicinal Chemistry, vol. 49, no. 14, pp. 4035–4043, 2006.
[59]
K. G. Hofbauer, A.-C. Lecourt, and J.-C. Peter, “Antibodies as pharmacologic tools for studies on the regulation of energy balance,” Nutrition, vol. 24, no. 9, pp. 791–797, 2008.
[60]
J.-C. Peter, G. Zipfel, A.-C. Lecourt, A. Bekel, and K. G. Hofbauer, “Antibodies raised against different extracellular loops of the melanocortin-3 receptor affect energy balance and autonomic function in rats,” Journal of Receptors and Signal Transduction, vol. 30, no. 6, pp. 444–453, 2010.
[61]
A. O. Shpakov, “Signal protein-derived peptides as functional probes and regulators of intracellular signaling,” Journal of Amino Acids, vol. 2011, Article ID 656051, 25 pages, 2011.
[62]
A. O. Shpakov, “Peptides derived from the extracellular loop of receptors: structure, mechanisms of action and application in physiology and medicine,” Russian The Journal of Physiology, vol. 97, no. 5, pp. 441–458, 2011.
[63]
C. P. Gilman, T. A. Perry, K. Furukawa, N. H. Grieg, J. M. Egan, and M. P. Mattson, “Glucagon-like peptide 1 modulates calcium responses to glutamate and membrane depolarization in hippocampal neurons,” Journal of Neurochemistry, vol. 87, no. 5, pp. 1137–1144, 2003.
[64]
A. Hamilton and C. Holscher, “Receptors for the insulin-like peptide GLP-1 are expressed on neurons in the CNS,” Neuroreport, vol. 20, no. 13, pp. 1161–1166, 2009.
[65]
A. Hamilton, S. Patterson, D. Porter, V. A. Gault, and C. Holscher, “Novel GLP-1 mimetics developed to treat type 2 diabetes promote progenitor cell proliferation in the brain,” Journal of Neuroscience Research, vol. 89, no. 4, pp. 481–489, 2011.
[66]
M. E. Doyle and J. M. Egan, “Mechanisms of action of glucagon-like peptide 1 in the pancreas,” Pharmacology & Therapeutics, vol. 113, no. 3, pp. 546–593, 2007.
[67]
J. A. Lovshin and D. J. Drucker, “Incretin-based therapies for type 2 diabetes mellitus,” Nature Reviews Endocrinology, vol. 5, no. 5, pp. 262–269, 2009.
[68]
J. J. Holst, R. Burcelin, and E. Nathanson, “Neuroprotective properties of GLP-1: theoretical and practical applications,” Current Medical Research and Opinion, vol. 27, no. 3, pp. 547–558, 2011.
[69]
P. L. McClean, V. A. Gault, P. Harriott, and C. H？lscher, “Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: a link between diabetes and Alzheimer's disease,” European Journal of Pharmacology, vol. 630, no. 1–3, pp. 158–162, 2010.
[70]
B. D. Green and P. R. Flatt, “Incretin hormone mimetics and analogues in diabetes therapeutics,” Best Practice and Research in Clinical Endocrinology and Metabolism, vol. 21, no. 4, pp. 497–516, 2007.
[71]
B. Botia, M. Basille, A. Allais et al., “Neurotrophic effects of PACAP in the cerebellar cortex,” Peptides, vol. 28, no. 9, pp. 1746–1752, 2007.
[72]
A. Tamas, D. Reglodi, O. Farkas et al., “Effect of PACAP in central and peripheral nerve injuries,” International Journal of Molecular Sciences, vol. 13, no. 7, pp. 8430–8448, 2012.
[73]
A. Dejda, P. Soko？owska, and J. Z. Nowak, “Neuroprotective potential of three neuropeptides PACAP, VIP and PHI,” Pharmacological Reports, vol. 57, no. 3, pp. 307–320, 2005.
[74]
S. Bourgault, D. Chatenet, O. Wurtz et al., “Strategies to convert PACAP from a hypophysiotropic neurohormone into a neuroprotective drug,” Current Pharmaceutical Design, vol. 17, no. 10, pp. 1002–1024, 2011.
[75]
S. Mansouri, H. Orts？ter, O. Pintor Gallego, V. Darsalia, ？. Sj？holm, and C. Patrone, “Pituitary adenylate cyclase-activating polypeptide counteracts the impaired adult neural stem cell viability induced by palmitate,” Journal of Neuroscience Research, vol. 90, no. 4, pp. 759–768, 2012.
[76]
A. Stengel, J. Rivier, and Y. Taché, “Central actions of somatostatin-28 and oligosomatostatin agonists to prevent components of the endocrine, autonomic and visceral responses to stress through interaction with different somatostatin receptor subtypes,” Current Pharmaceutical Design, vol. 19, no. 1, pp. 98–105, 2013.
[77]
A. D. Blake, A. C. Badway, and M. Z. Strowski, “Delineating somatostatin's neuronal actions,” Current Drug Targets, vol. 3, no. 2, pp. 153–160, 2004.
[78]
M. K. Tallent, “Somatostatin in the dentate gyrus,” Progress in Brain Research, vol. 163, pp. 265–284, 2007.
[79]
L. J. Hofland, R. A. Feelders, W. W. de Herder, and S. W. J. Lamberts, “Pituitary tumours: the sst/D2 receptors as molecular targets,” Molecular and Cellular Endocrinology, vol. 326, no. 1-2, pp. 89–98, 2010.
[80]
U. Kumar and M. Grant, “Somatostatin and somatostatin receptors,” Results and Problems in Cell Differentiation, vol. 50, pp. 137–184, 2010.
[81]
J. F. Bruno, Y. Xu, J. Song, and M. Berelowitz, “Pituitary and hypothalamic somatostatin receptor subtype messenger ribonucleic acid expression in the food-deprived and diabetic rat,” Endocrinology, vol. 135, no. 5, pp. 1787–1792, 1994.
[82]
V. Chavali, S. C. Tyagi, and P. K. Mishra, “Predictors and prevention of diabetic cardiomyopathy,” Diabetes, Metabolic Syndrome and Obesity, vol. 6, pp. 151–160, 2013.
[83]
P. Jourdon and D. Feuvray, “Calcium and potassium currents in ventricular myocytes isolated from diabetic rats,” The Journal of Physiology, vol. 470, pp. 411–429, 1993.
[84]
A. Picchi, S. Capobianco, T. Qiu et al., “Coronary microvascular dysfunction in diabetes mellitus: a review,” World Journal of Cardiology, vol. 2, no. 11, pp. 377–390, 2010.
[85]
I. Berlin, A. Grimaldi, F. Bosquet, and A. J. Puech, “Decreased β-adrenergic sensitivity in insulin-dependent diabetic subjects,” Journal of Clinical Endocrinology and Metabolism, vol. 63, no. 1, pp. 262–265, 1986.
[86]
U. D. Dincer, K. R. Bidasee, S. Guner, A. Tay, A. T. Oz？elikay, and V. M. Altan, “The effect of diabetes on expression of β1-, β2- and β3-adrenoreceptors in rat hearts,” Diabetes, vol. 50, pp. 455–461, 2001.
[87]
K. Watanabe, R. A. Thandavarayan, M. Harima et al., “Role of differential signaling pathways and oxidative stress in diabetic cardiomyopathy,” Current Cardiology Reviews, vol. 6, no. 4, pp. 280–290, 2010.
[88]
C. Gauthier, G. Tavernier, F. Charpentier, D. Langin, and H. Le Marec, “Functional β3-adrenoceptor in the human heart,” The Journal of Clinical Investigation, vol. 98, no. 2, pp. 556–562, 1996.
[89]
M. G. Ursino, V. Vasina, E. Raschi, F. Crema, and F. De Ponti, “The β3-adrenoceptor as a therapeutic target: current perspectives,” Pharmacological Research, vol. 59, no. 4, pp. 221–234, 2009.
[90]
A. Kashiwaga, Y. Nishio, Y. Saeki, Y. Kida, M. Kodama, and Y. Shigeta, “Plasma membrane-specific deficiency in cardiac β-adrenergic receptor in streptozotocin-diabetic rats,” The American Journal of Physiology, vol. 257, no. 2, part 1, pp. 127–132, 1989.
[91]
K. Saito, A. Kuroda, and H. Tanaka, “Characterisation of β1 and β2 adrenoceptor subtypes in the atrioventricular node of diabetic rat hearts by quantitative autoradiography,” Cardiovascular Research, vol. 25, no. 11, pp. 950–954, 1991.
[92]
S. Gando, Y. Hattori, Y. Akaishi, J. Nishihira, and M. Kanno, “Impaired contractile response to beta adrenoceptor stimulation in diabetic rat hearts: alterations in beta adrenoceptors-G protein-adenylate cyclase system and phospholamban phosphorylation,” The Journal of Pharmacology and Experimental Therapeutics, vol. 282, no. 1, pp. 475–484, 1997.
[93]
N. Matsuda, Y. Hattori, S. Gando, Y. Akaishi, O. Kemmotsu, and M. Kanno, “Diabetes-induced down-regulation of β1-adrenoceptor mRNA expression in rat heart,” Biochemical Pharmacology, vol. 58, no. 5, pp. 881–885, 1999.
[94]
P. R. Sundaresan, V. K. Sharma, S. I. Gingold, and S. P. Banerjee, “Decreased β-adrenergic receptors in rat heart in streptozotocin-induced diabetes: role of thyroid hormones,” Endocrinology, vol. 114, no. 4, pp. 1358–1363, 1984.
[95]
S. Moniotte, L. Kobzik, O. Feron, J.-N. Trochu, C. Gauthier, and J.-L. Balligand, “Upregulation of β3-adrenoceptors and altered contractile response to inotropic amines in human failing myocardium,” Circulation, vol. 103, no. 12, pp. 1649–1655, 2001.
[96]
B. Rozec and C. Gauthier, “β3-adrenoceptors in the cardiovascular system: putative roles in human pathologies,” Pharmacology and Therapeutics, vol. 111, no. 3, pp. 652–673, 2006.
[97]
J. Walston, K. Silver, C. Bogardus et al., “Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the β3-adrenergic-receptor gene,” The New England Journal of Medicine, vol. 333, no. 6, pp. 343–347, 1995.
[98]
L.-L. Xiu, J.-P. Weng, Y. Sui, J. Wang, J.-H. Yan, and Z.-M. Huang, “Common variants in beta 3-adrenergic-receptor and uncoupling protein-2 genes are associated with type 2 diabetes and obesity,” Zhonghua Yi Xue Za Zhi, vol. 84, no. 5, pp. 375–379, 2004.
[99]
N. Sakane, T. Yoshida, K. Yoshioka et al., “β3-adrenoreceptor gene polymorphism: a newly identified risk factor for proliferative retinopathy in NIDDM patients,” Diabetes, vol. 46, no. 10, pp. 1633–1636, 1997.
[100]
N. Sakane, T. Yoshida, K. Yoshioka et al., “Trp64 Arg mutation of β3-adrenoceptor gene is associated with diabetic nephropathy in type II diabetes mellitus,” Diabetologia, vol. 41, no. 12, pp. 1533–1534, 1998.
[101]
A. Wichelhaus, M. Russ, S. Petersen, and J. Eckel, “G protein expression and adenylate cyclase regulation in ventricular cardiomyocytes from STZ-diabetic rats,” The American Journal of Physiology, vol. 267, no. 2, pp. H548–H555, 1994.
[102]
C. Communal, K. Singh, D. B. Sawyer, and W. S. Colucci, “Opposing effects of β1- and β2-adrenergic receptors on cardiac myocyte apoptosis: role of a pertussis toxin-sensitive G protein,” Circulation, vol. 100, no. 22, pp. 2210–2212, 1999.
[103]
ü. D. Din？er, A. Onay, N. Ari, A. T. ？z？elikay, and V. M. Altan, “The effects of diabetes on β-adrenoceptor mediated responsiveness of human and rat atria,” Diabetes Research and Clinical Practice, vol. 40, no. 2, pp. 113–122, 1998.
[104]
K. Kamata, T. Satoh, H. Tanaka, and K. Shigenobu, “Changes in electrophysiological and mechanical responses of the rat papillary muscle to α- and β-agonist in streptozotocin-induced diabetes,” Canadian The Journal of Physiology and Pharmacology, vol. 75, no. 7, pp. 781–788, 1997.
[105]
A. Michel, G. H. Cros, J. H. McNeil, and J. J. Serrano, “Cardiac adenylate cyclase activity in streptozotocin-treated rats after 4 months of diabetes: impairment of epinephrine and glucagon stimulation,” Life Sciences, vol. 37, no. 22, pp. 2067–2075, 1985.
[106]
G. Plourde, M. Martin, S. Rousseau-Migneron, and A. Nadeau, “Effect of physical training on ventricular β-adrenergic receptor adenylate cyclase system of diabetic rats,” Metabolism, vol. 40, no. 4, pp. 362–367, 1991.
[107]
L. X. Fu, C. H. Bergh, Q. M. Liang et al., “Diabetes-induced changes in the Gi-modulated muscarinic receptor-adenylyl cyclase system in rat myocardium,” Pharmacology & Toxicology, vol. 75, no. 3-4, pp. 186–193, 1994.
[108]
T. Matsumoto, K. Wakabayashi, T. Kobayashi, and K. Kamata, “Functional changes in adenylyl cyclases and associated decreases in relaxation responses in mesenteric arteries from diabetic rats,” The American Journal of Physiology, vol. 289, no. 5, pp. H2234–H2243, 2005.
[109]
S. F. Vatner, M. Park, L. Yan et al., “Adenylyl cyclase type 5 in cardiac disease, metabolism, and aging,” The American Journal of Physiology, vol. 305, no. 1, pp. H1–H8, 2013.
[110]
P. K. Ganguly, R. E. Beamish, and K. S. Dhalla, “Norepinephrine storage, distribution, and release in diabetic cardiomyopathy,” The American Journal of Physiology, vol. 252, no. 6, p. 15/6, 1987.
[111]
K. R. Bidasee, H. Zheng, C.-H. Shao, S. K. Parbhu, G. J. Rozanski, and K. P. Patel, “Exercise training initiated after the onset of diabetes preserves myocardial function: effects on expression of β-adrenoceptors,” Journal of Applied Physiology, vol. 105, no. 3, pp. 907–914, 2008.
[112]
S. L. D. Lahaye, A. Gratas-Delamarche, L. Malardé et al., “Intense exercise training induces adaptation in expression and responsiveness of cardiac β-adrenoceptors in diabetic rats,” Cardiovascular Diabetology, vol. 9, article 72, 2010.
[113]
S. W. Schaffer, S. Allo, S. Punna, and T. White, “Defective response to cAMP-dependent protein kinase in non-insulin-dependent diabetic heart,” The American Journal of Physiology, vol. 261, no. 3, pp. E369–E376, 1991.
[114]
O. H. M. Beenen, H. D. Batink, M. Pfaffendorf, and P. A. van Zwieten, “β-adrenoceptors in the hearts of diabetic-hypertensive rats: radioligand binding and functional experiments,” Blood Pressure, vol. 6, no. 1, pp. 44–51, 1997.
[115]
W. C. Stanley, J. J. Dore, J. L. Hall, C. D. Hamilton, R. D. Pizzurro, and D. A. Roth, “Diabetes reduces right atrial β-adrenergic signaling but not agonist stimulation of heart rate in swine,” Canadian Journal of Physiology and Pharmacology, vol. 79, no. 4, pp. 346–351, 2001.
[116]
A. Bilginoglu, F. Amber Cicek, M. Ugur, H. Gurdal, and B. Turan, “The role of gender differences in beta-adrenergic receptor responsiveness of diabetic rat heart,” Molecular and Cellular Biochemistry, vol. 305, no. 1-2, pp. 63–69, 2007.
[117]
V. Regitz-Zagrosek, S. Oertelt-Prigione, U. Seeland, and R. Hetzer, “Sex and gender differences in myocardial hypertrophy and heart failure,” Circulation Journal, vol. 74, no. 7, pp. 1265–1273, 2010.
[118]
C. E. Heyliger, G. N. Pierce, and P. K. Singal, “Cardiac alpha- and beta-adrenergic receptor alterations in diabetic cardiomyopathy,” Basic Research in Cardiology, vol. 77, no. 6, pp. 610–618, 1982.
[119]
J. Latifpour and J. H. McNeill, “Cardiac autonomic receptors: effect of long-term experimental diabetes,” The Journal of Pharmacology and Experimental Therapeutics, vol. 230, no. 1, pp. 242–249, 1984.
[120]
M. Wald, E. S. Borda, and L. Sterin-Borda, “α-Adrenergic supersensitivity and decreased number of α-adrenoceptors in heart from acute diabetic rats,” Canadian Journal of Physiology and Pharmacology, vol. 66, no. 9, pp. 1154–1160, 1988.
[121]
S. E. Downing, J. C. Lee, and R. R. Fripp, “Enhanced sensitivity of diabetic hearts to alpha-adrenoceptor stimulation,” The American Journal of Physiology, vol. 245, no. 5, part 1, pp. H808–813, 1983.
[122]
J. B. Heijnis and P. A. van Zwieten, “Enhanced inotropic responsiveness to α1-adrenoceptor stimulation in isolated working hearts from diabetic rats,” Journal of Cardiovascular Pharmacology, vol. 20, no. 4, pp. 559–562, 1992.
[123]
S. Setty, W. Sun, R. Martinez, H. F. Downey, and J. D. Tune, “α-adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in experimental diabetes mellitus,” Journal of Applied Physiology, vol. 97, no. 1, pp. 431–438, 2004.
[124]
K. Kamata, T. Satoh, T. Matsumoto et al., “Enhancement of methoxamine-induced contractile responses of rat ventricular muscle in streptozotocin-induced diabetes is associated with α1A adrenoceptor upregulation,” Acta Physiologica, vol. 188, no. 3-4, pp. 173–183, 2006.
[125]
S. Gao, Y.-B. Oh, A. Shah, W. H. Park, and S. H. Kim, “Suppression of ANP secretion by somatostatin through somatostatin receptor type 2,” Peptides, vol. 32, no. 6, pp. 1179–1186, 2011.
[126]
S. Hashim, Y. Li, A. Nagakura, S. Takeo, and M. B. Anand-Srivastava, “Modulation of G-protein expression and adenylyl cyclase signaling by high glucose in vascular smooth muscle,” Cardiovascular Research, vol. 63, no. 4, pp. 709–718, 2004.
[127]
S. Hashim, Y. Y. Liu, R. Wang, and M. B. Anand-Srivastava, “Streptozotocin-induced diabetes impairs G-protein linked signal transduction in vascular smooth muscle,” Molecular and Cellular Biochemistry, vol. 240, no. 1-2, pp. 57–65, 2002.
[128]
Y. Li, M. Descorbeth, and M. B. Anand-Srivastava, “Role of oxidative stress in high glucose-induced decreased expression of Giα proteins and adenylyl cyclase signaling in vascular smooth muscle cells,” The American Journal of Physiology, vol. 294, no. 6, pp. H2845–H2854, 2008.
[129]
M. Descorbeth and M. B. Anand-Srivastava, “Role of oxidative stress in high-glucose- and diabetes-induced increased expression of Gq/11α proteins and associated signaling in vascular smooth muscle cells,” Free Radical Biology and Medicine, vol. 49, no. 9, pp. 1395–1405, 2010.
[130]
A. Ozuari, Y. Ozturk, N. Yildizoglu-Ari, A. T. Ozcelikay, and V. M. Altan, “The effects of glyburide and insulin on the cardiac performance in rats with non-insulin-dependent diabetes mellitus,” General Pharmacology, vol. 24, no. 1, pp. 165–169, 1993.
[131]
T. Bányász, I. Kalapos, S. Z. Kelemen, and T. Kovács, “Changes in cardiac contractility in IDDM and NIDDM diabetic rats,” General Physiology and Biophysics, vol. 15, no. 5, pp. 357–369, 1996.
[132]
B. Huisamen, E. Marais, S. Genade, and A. Lochner, “Serial changes in the myocardial β-adrenergic signalling system in two models of non-insulin dependent diabetes mellitus,” Molecular and Cellular Biochemistry, vol. 219, no. 1-2, pp. 73–82, 2001.
[133]
P. K. Mishra, O. Awe, N. Metreveli, N. Qipshidze, I. G. Joshua, and S. C. Tyagi, “Exercise mitigates homocysteine - β2-adrenergic receptor interactions to ameliorate contractile dysfunction in diabetes,” International Journal of Physiology, Pathophysiology and Pharmacology, vol. 3, no. 2, pp. 97–106, 2011.
[134]
A. J. Garber, “The impact of streptozotocin-induced diabetes mellitus on cyclic nucleotide regulation of skeletal muscle amino acid metabolism in the rat,” The Journal of Clinical Investigation, vol. 65, no. 2, pp. 478–487, 1980.
[135]
G. Plourde, S. Rousseau-Migneron, and A. Nadeau, “Physical training increases β-adrenoceptor density and adenylate cyclase activity in high-oxidative skeletal muscle of diabetic rats,” Metabolism, vol. 41, no. 12, pp. 1331–1335, 1992.
[136]
G. Plourde, S. Rousseau-Migneron, and A. Nadeau, “Effect of endurance training on β-adrenergic system in three different skeletal muscles,” Journal of Applied Physiology, vol. 74, no. 4, pp. 1641–1646, 1993.
[137]
A. O. Shpakov, L. A. Kuznetsova, S. A. Plesneva et al., “Functional defects in adenylyl cyclase signaling mechanisms of insulin and relaxin in skeletal muscles of rat with streptozotocin type 1 diabetes,” Central European Journal of Biology, vol. 1, no. 4, pp. 530–544, 2006.
[138]
X.-L. Zheng, J. H. Guo, H.-Y. Wang, and C. C. Malbon, “Expression of constitutively activated G(iα2) in vivo ameliorates streptozotocininduced diabetes,” The Journal of Biological Chemistry, vol. 273, no. 37, pp. 23649–23651, 1998.
[139]
X. Song, X. Zheng, C. C. Malbon, and H.-Y. Wang, “Gαi2 enhances in vivo activation of and insulin signaling to GLUT4,” The Journal of Biological Chemistry, vol. 276, no. 37, pp. 34651–34658, 2001.
[140]
T. M. Chan, J. P. Dehaye, and A. Tatoyan, “Activation of lipolysis by epinephrine and electrical stimulation in the perfused hindquarters of lean and obese-diabetic (db/db) mice,” Biochimica et Biophysica Acta, vol. 751, no. 3, pp. 384–392, 1983.
[141]
R. R. Dighe, F. J. Rojas, L. Birnbaumer, and A. J. Garber, “Glucagon-stimulable adenylyl cyclase in rat liver. The impact of streptozotocin-induced diabetes mellitus,” The Journal of Clinical Investigation, vol. 73, no. 4, pp. 1013–1023, 1984.
[142]
M. Bushfield, S. L. Griffiths, G. J. Murphy et al., “Diabetes-induced alterations in the expression, functioning and phosphorylation state of the inhibitory guanine nucleotide regulatory protein Gi2 in hepatocytes,” The Biochemical Journal, vol. 271, no. 2, pp. 365–372, 1990.
[143]
M. D. Housley, “Gi2 is at the centre of an active phosphorylation/dephosphorylation cycle in hepatocytes: the fine-tuning of stimulatory and inhibitory inputs into adenylate cyclase in normal and diabetic states,” Cellular Signalling, vol. 3, no. 1, pp. 1–9, 1991.
[144]
N. J. Morris, M. Bushfield, and M. D. Houslay, “Streptozotocin-induced diabetes elicits the phosphorylation of hepatocyte Gi2α at the protein kinase C site but not at the protein kinase A-controlled site,” The Biochemical Journal, vol. 315, no. 2, pp. 417–420, 1996.
[145]
S. Shima, H. Fukase, and N. Akamatsu, “Adrenergic receptors and adenylate cyclase activity in hepatocytes of the streptozotocin-diabetic rat,” Endocrinologia Japonica, vol. 39, no. 2, pp. 157–163, 1992.
[146]
N. Bégin-Heick, “Liver β-adrenergic receptors, G proteins, and adenylyl cyclase activity in obesity-diabetes syndromes,” The American Journal of Physiology, vol. 266, no. 6, part 1, pp. C1664–C1672, 1994.
[147]
N. Begin-Heick, “α-Subunits of Gs and Gi in adipocyte plasma membranes of genetically diabetic (db/db) mice,” The American Journal of Physiology, vol. 263, no. 1, part 1, pp. C121–C129, 1992.
[148]
N. McFarlane-Anderson, J. Bailly, and N. Begin-Heick, “Levels of G-proteins in liver and brain of lean and obese (ob/ob) mice,” The Biochemical Journal, vol. 282, no. 1, pp. 15–23, 1992.
[149]
T. M. Palmer and M. D. Houslay, “Determination of G-protein levels, ADP-ribosylation by cholera and pertussis toxins and the regulation of adenylyl cyclase activity in liver plasma membrane from lean and genetically diabetic (db/db) mice,” Biochimica et Biophysica Acta, vol. 1097, no. 3, pp. 193–204, 1991.
[150]
P. Young, D. M. Kirkham, G. J. Murphy, and M. A. Cawthorne, “Evaluation of inhibitory guanine nucleotide regulatory protein Gi function in hepatocyte and liver membranes from obese Zucker (fa/fa) rats and their lean (Fa/?) littermates,” Diabetologia, vol. 34, no. 8, pp. 565–569, 1991.
[151]
D. M. Kirkham, G. J. Murphy, and P. Young, “Demonstration of inhibitory guanine nucleotide regulatory protein (Gi) function in liver and hepatocyte membranes from streptozotocin-treated rats,” The Biochemical Journal, vol. 284, no. 2, pp. 301–304, 1992.
[152]
L. Madsen and K. Kristiansen, “The importance of dietary modulation of cAMP and insulin signaling in adipose tissue and the development of obesity,” Annals of the New York Academy of Sciences, vol. 1190, pp. 1–14, 2010.
[153]
S. Collins, K. W. Daniel, A. E. Petro, and R. S. Surwit, “Strain-specific response to β3-adrenergic receptor agonist treatment of diet-induced obesity in mice,” Endocrinology, vol. 138, no. 1, pp. 405–413, 1997.
[154]
P. Muzzin, J.-P. Revelli, F. Kuhne et al., “An adipose tissue-specific β-adrenergic receptor. Molecular cloning and down-regulation in obesity,” The Journal of Biological Chemistry, vol. 266, no. 35, pp. 24053–24058, 1991.
[155]
S. Collins, K. W. Daniel, E. M. Rohlfs, V. Ramkumar, I. L. Taylor, and T. W. Gettys, “Impaired expression and functional activity of the β3- and β1-adrenergic receptors in adipose tissue of congenitally obese (C57BL/6J ob/ob) mice,” Molecular Endocrinology, vol. 8, no. 4, pp. 518–527, 1994.
[156]
N. Bégin-Heick, “β-adrenergic receptors and G-proteins in the ob/ob mouse,” International Journal of Obesity, vol. 20, no. 3, pp. S32–S35, 1996.
[157]
T. W. Gettys, P. M. Watson, I. L. Taylor, and S. Collins, “RU-486 (Mifepristone) ameliorates diabetes but does not correct deficient β-adrenergic signalling in adipocytes from mature C57BL/6J-ob/ob mice,” International Journal of Obesity, vol. 21, no. 10, pp. 865–873, 1997.
[158]
B. A. Evans, M. Papaioannou, F. Anastasopoulos, and R. J. Summers, “Differential regulation of β3-adrenoceptors in gut and adipose tissue of genetically obese (ob/ob) C57BL/6J-mice,” British Journal of Pharmacology, vol. 124, no. 4, pp. 763–771, 1998.
[159]
A. K. Dhalla, M. Santikul, J. M. Chisholm, L. Belardinelli, and G. M. Reaven, “Comparison of the antilipolytic effects of an A1 adenosine receptor partial agonist in normal and diabetic rats,” Diabetes, Obesity and Metabolism, vol. 11, no. 2, pp. 95–101, 2009.
[160]
J. Vendrell, R. El Bekay, B. Peral et al., “Study of the potential association of adipose tissue GLP-1 receptor with obesity and insulin resistance,” Endocrinology, vol. 152, no. 11, pp. 4072–4079, 2011.
[161]
R. L. Rodgers, “Glucagon and cyclic AMP: time to turn the page?” Current Diabetes Reviews, vol. 8, no. 5, pp. 362–381, 2012.
[162]
A. K. Dhalla, J. W. Chisholm, G. M. Reaven, and L. Belardinelli, “A1 adenosine receptor: role in diabetes and obesity,” Handbook of Experimental Pharmacology, vol. 193, pp. 271–295, 2009.
[163]
D. Strassheim, G. Milligan, and M. D. Houslay, “Diabetes abolishes the GTP-dependent, but not the receptor-dependent inhibitory function of the inhibitory guanine-nucleotide-binding regulatory protein (Gi) on adipocyte adenylate cyclase activity,” The Biochemical Journal, vol. 266, no. 2, pp. 521–526, 1990.
[164]
J. C. Weems, B. A. Griesel, and A. L. Olson, “Class II histone deacetylases downregulate GLUT4 transcription in response to increased cAMP signaling in cultured adipocytes and fasting mice,” Diabetes, vol. 61, no. 6, pp. 1404–1414, 2012.
[165]
S. J. Bonasera and L. H. Tecott, “Mouse models of serotonin receptor function: toward a genetic dissection of serotonin systems,” Pharmacology and Therapeutics, vol. 88, no. 2, pp. 133–142, 2000.
[166]
L. K. Heisler, M. A. Cowley, L. H. Tecott et al., “Activation of central melanocortin pathways by fenfluramine,” Science, vol. 297, no. 5581, pp. 609–611, 2002.
[167]
A. R. Cole, A. Astell, C. Green, and C. Sutherland, “Molecular connexions between dementia and diabetes,” Neuroscience and Biobehavioral Reviews, vol. 31, no. 7, pp. 1046–1063, 2007.
[168]
L. Zhou, G. M. Sutton, J. J. Rochford et al., “Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways,” Cell Metabolism, vol. 6, no. 5, pp. 398–405, 2007.
[169]
S. M. de La Monte, M. Tong, V. Nguyen, M. Setshedi, L. Longato, and J. R. Wands, “Ceramide-mediated insulin resistance and impairment of cognitive-motor functions,” Journal of Alzheimer's Disease, vol. 21, no. 3, pp. 967–984, 2010.
[170]
M. A. L. van Tilburg, C. C. McCaskill, J. D. Lane et al., “Depressed mood is a factor in glycemic control in type 1 diabetes,” Psychosomatic Medicine, vol. 63, no. 4, pp. 551–555, 2001.
[171]
P. J. Lustman and R. E. Clouse, “Depression in diabetic patients: the relationship between mood and glycemic control,” Journal of Diabetes and Its Complications, vol. 19, no. 2, pp. 113–122, 2005.
[172]
J. L. Kerr, E. M. Timpe, and K. A. Petkewicz, “Bromocriptine mesylate for glycemic management in type 2 diabetes mellitus,” The Annals of Pharmacotherapy, vol. 44, no. 11, pp. 1777–1785, 2010.
[173]
D. S. Bell, “Focusing on cardiovascular disease in type 2 diabetes mellitus: an introduction to bromocriptine QR,” Postgraduate Medicine, vol. 124, no. 5, pp. 121–135, 2012.
[174]
R. Scranton and A. Cincotta, “Bromocriptine unique formulation of a dopamine agonist for the treatment of type 2 diabetes,” Expert Opinion on Pharmacotherapy, vol. 11, no. 2, pp. 269–279, 2010.
[175]
N. Mikhail, “Quick-release bromocriptine for treatment of type 2 diabetes,” Current Drug Delivery, vol. 8, no. 5, pp. 511–516, 2011.
