Improvement of Hyperphagia by Activation of Cerebral I1-Imidazoline Receptors in Streptozotocin-induced Diabetic Mice

H. H. Chung; T. T. Yang; M. F. Chen; M. T. Chou; J. T. Cheng

doi:10.1055/s-0032-1314835

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2012; 44(09): 645-649
DOI: 10.1055/s-0032-1314835

Original Basic

Improvement of Hyperphagia by Activation of Cerebral I₁-Imidazoline Receptors in Streptozotocin-induced Diabetic Mice

H. H. Chung

¹Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan

,

T. T. Yang

²Department of Pathology, School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung City, Taiwan

,

M. F. Chen

³Department of Nursing and Biotechnology, Chung Hwa University of Medical Technology, Jen-Te, Tainan City, Taiwan

,

M. T. Chou

⁴Department of Cardiology and Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan

,

J. T. Cheng

¹Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan

⁴Department of Cardiology and Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City, Taiwan

⁵Institute of Medical Science, College of Health Science, Chang Jung Christian University, Guei-Ren, Tainan City, Taiwan

› Institutsangaben

Abstract

Imidazoline I₁-receptors (I₁R) are known to regulate blood pressure and rilmenidine, an agonist, is widely used as antihypertensive agent in clinic. However, the role of I₁R in feeding behavior is still unclear. In the present study, we used the agonist of I₁R to investigate the effect on hyperphagia in streptozotocin (STZ)-induced diabetic mice. Rilmenidine decreased the food intake of STZ-diabetic mice in a dose-dependent manner. The reduction of food intake was abolished by pretreatment with efaroxan at the dose sufficient to block I₁R. Intracerebroventricular (icv) administration of rilmenidine into STZ-diabetic mice also significantly reduced hyperphagia, which was reversed by icv administration of efaroxan. In addition, similar results were observed in STZ-diabetic mice, which received chronic treatment with rilmenidine 3 times daily (t.i.d.) for 7 days. Moreover, the hypothalamic neuropeptide Y (NPY) level was reduced by rilmenidine that was also reversed by pretreatment with efaroxan. In conclusion, the obtained results suggest that rilmenidine can decrease food intake in STZ-diabetic mice through an activation of I₁R to lower hypothalamic NPY level.

Key words

feeding - hyperphagia - imidazoline I₁-receptors - neuropeptide Y - STZ-diabetic mice

Volltext

Referenzen

References
1 Arora S Anubhuti. Role of neuropeptides in appetite regulation and obesity–a review. Neuropeptides 2006; 40: 375-401
2 Williams G, Bing C, Cai XJ, Harrold JA, King PJ, Liu XH. The hypothalamus and the control of energy homeostasis: different circuits, different purposes. Physiol Behav 2001; 74: 683-701
3 Kuo DY. Hypothalamic neuropeptide Y (NPY) and the attenuation of hyperphagia in streptozotocin diabetic rats treated with dopamine D1/D2 agonists. Br J Pharmacol 2006; 148: 640-647
4 Shin MS, Kim H, Chang HK, Lee TH, Jang MH, Shin MC, Lim BV, Lee HH, Kim YP, Yoon JH, Jeong IG, Kim CJ. Treadmill exercise suppresses diabetes-induced increment of neuropeptide Y expression in the hypothalamus of rats. Neurosci Lett 2003; 346: 157-160
5 Verhulst PJ, De Smet B, Saels I, Thijs T, Ver Donck L, Moechars D, Peeters TL, Depoortere I. Role of ghrelin in the relationship between hyperphagia and accelerated gastric emptying in diabetic mice. Gastroenterology 2008; 135: 1267-1276
6 Kojima S, Asakawa A, Amitani H, Sakoquchi T, Ueno N, Inui A, Kalra SP. Central leptin gene therapy, a substitute for insulin therapy to ameliorate hyperglycemia and hyperphagia, and promote survival in insulin-deficient diabetic mice. Peptides 2009; 30: 962-966
7 Ernsberger P, Friedman JE, Koletsky RJ. The I1-imidazoline receptor: from binding site to therapeutic target in cardiovascular disease. J Hypertens Suppl 1997; 15: S9-S23
8 Koletsky RJ, Velliquette RA, Ernsberger P. The role of I(1)-imidazoline receptors and alpha(2)-adrenergic receptors in the modulation of glucose and lipid metabolism in the SHROB model of metabolic syndrome X. Ann N Y Acad Sci 2003; 1009: 251-261
9 Niu CS, Wu HT, Cheng KC, Lin KC, Chen CT, Cheng JT. A novel mechanism for decreasing plasma lipid level from imidazoline I-1 receptor activation in high fat diet-fed mice. Horm Metab Res 2011; 43: 458-463
10 Gongadze NV, Antelava NA, Kezeli TD. Imidazoline receptors. Georgian Med News 2008; 44-47
11 Head GA, Mayorov DN. Imidazoline receptors, novel agents and therapeutic potential. Cardiovasc Hematol Agents Med Chem 2006; 4: 17-32
12 Head GA, Burke SL, Chan CK. Site and receptors involved in the sympathoinhibitory actions of rilmenidine. J Hypertens Suppl 1998; 16: S7-S12
13 Ko WC, Liu IM, Chung HH, Cheng JT. Activation of I(2)-imidazoline receptors may ameliorate insulin resistance in fructose-rich chow-fed rats. Neurosci Lett 2008; 448: 90-93
14 Su CH, Liu IM, Chung HH, Cheng JT. Activation of I2-imidazoline receptors by agmatine improved insulin sensitivity through two mechanisms in type-2 diabetic rats. Neurosci Lett 2009; 457: 125-128
15 Morgan NG, Chan SL. Imidazoline binding sites in the endocrine pancreas: can they fulfil their potential as targets for the development of new insulin secretagogues?. Curr Pharm Des 2001; 7: 1413-1431
16 Dupuy O, Bauduceau B, Mayaudon H. Efficacy of rilmenidine, a selective I1 imidazoline receptor binding agent in diabetic hypertensive patients. Am J Hypertens 2000; 13: 123S-126S
17 Meredith PA, Reid JL. Efficacy and tolerability of long-term rilmenidine treatment in hypertensive diabetic patients. A retrospective analysis of a general practice study. Am J Cardiovasc Drugs 2004; 4: 195-200
18 Hayashi K, Kojima R, Ito M. Strain differences in the diabetogenic activity of streptozotocin in mice. Biol Pharm Bull 2006; 29: 1110-1119
19 Wellman PJ. Norepinephrine and the control of food intake. Nutrition 2000; 16: 837-842
20 Lal H, Yaden S. Discriminative stimuli produced by clonidine in spontaneously hypertensive rats: generalization to antihypertensive drugs with different mechanisms of action. J Pharmacol Exp Ther 1985; 232: 33-39
21 Zhu QM, Lesnick JD, Jasper JR, MacLennan SJ, Dillon MP, Eglen RM, Blue Jr DR. Cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A-adrenoceptor transgenic mice. Br J Pharmacol 1999; 126: 1522-1530
22 Anderson NJ, Lupo PA, Nutt DJ, Hudson AL, Robinson ES. Characterisation of imidazoline I2 binding sites in pig brain. Eur J Pharmacol 2005; 519: 68-74
23 Meyer JH, Ginovart N, Boovariwala A, Sagratis S, Hussey D, Garcia A, Young T, Praschak-Rieder N, Wilson AA, Houle S. Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression. Arch Gen Psychiatry 2006; 63: 1209-1216
24 Matsumoto C, Shinkai T, Hori H, Ohmori O, Nakamura J. Polymorphisms of dopamine degradation enzyme (COMT and MAO) genes and tardive dyskinesia in patients with schizophrenia. Psychiatry Res 2004; 127: 1-7
25 El-Mas MM, El-Gowelli HM, Ghazal AR, Harraz OF, Mohy EI-Din MM. Facilitation of central imidazoline I(1)-site/extracellular signal-regulated kinase/p38 mitogen-activated protein kinase signalling mediates the hypotensive effect of ethanol in rats with acute renal failure. Br J Pharmacol 2009; 158: 1629-1640
26 El-Mas MM, Abdel-Rahman AA. Evidence for the involvement of central I1 imidazoline receptor in ethanol counteraction of clonidine hypotension in spontaneously hypertensive rats. J Cardiovasc Pharmacol 2001; 38: 417-426
27 Thomas AJ, Erokwu BO, Yamamoto BK, Ernsberger P, Bishara O, Strohl KP. Alterations in respiratory behavior, brain neurochemistry and receptor density induced by pharmacologic suppression of sleep in the neonatal period. Brain Res Dev Brain Res 2000; 120: 181-189
28 Zhang J, Abdel-Rahman AA. Mitogen-activated protein kinase phosphorylation in the rostral ventrolateral medulla plays a key role in imidazoline (i1)-receptor-mediated hypotension. J Pharmacol Exp Ther 2005; 314: 945-952
29 Sindelar DK, Havel PJ, Seeley RJ, Wilkinson CW, Woods SC, Schwartz MW. Low plasma leptin levels contribute to diabetic hyperphagia in rats. Diabetes 1999; 48: 1275-1280
30 Hagemann D, Meier JJ, Gallwitz B, Schmidt WE. Appetite regulation by ghrelin – a novel neuro-endocrine gastric peptide hormone in the gut-brain-axis. Z Gastroenterol 2003; 41: 929-936
31 Gelling RW, Overduin J, Morrison CD, Morton GJ, Frayo RS, Cummings DE, Schwartz MW. Effect of uncontrolled diabetes on plasma ghrelin concentrations and ghrelin-induced feeding. Endocrinology 2004; 145: 4575-4582
32 Ishii S, Kamegai J, Tamura H, Shimizu T, Sugihara H, Oikawa S. Role of ghrelin in streptozotocin-induced diabetic hyperphagia. Endocrinology 2002; 143: 4934-4937
33 Mercer RE, Chee MJ, Colmers WF. The role of NPY in hypothalamic mediated food intake. Front Neuroendocrinol 2011; 32: 398-415
34 Frankish HM, Dryden S, Hopkins D, Wang Q, Williams G. Neuropeptide Y, the hypothalamus, and diabetes: insights into the central control of metabolism. Peptides 1995; 16: 757-771
35 Qu SY, Yang YK, Li JY, Zeng Q, Gantz I. Agouti-related protein is a mediator of diabetic hyperphagia. Regul Pept 2001; 98: 69-75
36 Sahu A, Sninsky CA, Kalra SP. Evidence that hypothalamic neuropeptide Y gene expression and NPY levels in the paraventricular nucleus increase before the onset of hyperphagia in experimental diabetes. Brain Res 1997; 755: 339-342
37 Liu IM, Chi TC, Cheng JT. Decrease of hypothalamic neuropeptide Y gene expression by vanadyl sulfate in streptozotocin-induced diabetic rats. Horm Metab Res 2001; 33: 96-100
38 Bing C, King P, Pickavance L, Brown M, Ziegler D, Kaan E, Williams G. The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones. Br J Pharmacol 1999; 127: 35-42