Treatment effect of GABA on improve type one diabetes in NOD mice

Transcript

1 Physiology and Pharmacology, 13 (3), Fall 2009 [rticle in Persian] Treatment effect of G on improve type one diabetes in NOD mice Nepton Soltani 1*, Mansoor Keshavarz 2, Qinghua Wang 3 1. Department of Physiology, Medical School, Hormozgan University of Medical Science, andarabas, Iran 2. Department of Physiology, Medical school, Tehran University of Medical Science, Tehran, Iran 3. Department of Endocrine and Metabolism, Toronto University, Toronto, Canada Received: 1 Oct 2009 ccepted: 18 Nov 2009 bstract* Introduction: Gama amino butyric acid (G) is the major inhibitory neurotransmitter in the mammalian nervous system. The concentration of G and the number of G cell secretion decrease in diabetic patient and experimental diabetes model. The reported effects of G activation on insulin secretion from beta cells have been controversial. In this study we investigated if G administration in animal diabetes model can change insulin and glucagon secretion and improve some diabetic symptoms. Methods: Twenty fourth-week old NOD mi(non obese diabetic mice) ce were used. Two months after diabetic induction animals were divided into the two groups. One group received 200 µmol of G and the other group received phosphate buffer solution (PS) for one month. Results: G administration could significantly decrease plasma glucose and glucagon level, water consumption and urine volume and body fat distribution in the mesenteric bed and abdominal wall. It also could increase plasma C- peptide level and it has not effect on food intake. Conclusion: NOD mice is very good genetically model for type one diabetes and G administration in this mice could treatment some of diabetic symptom. It seems may be we could use of G for treatment of diabetic symptom in future. Keywords: Type one diabetes, G, C-peptide, Glocagon, glucose, NOD mice. * Corresponding author e- mail: nsoltani@hums.ac.ir vailable

2 (3) Non Obese Diabetic 3 2 * : 88 9 :. : NOD.. NOD (Non obese diabetic mice) 20 : ( 0/1 ) (Phosphate uffer Solution)PS PS :.. C-Peptide. NOD :..NOD C-Peptide : [ ]. [16 13] * nsoltani@hums.ac.ir : * :

3 (Canada scensia ELITE XL metr) ).[20] ( ) 10 [ ] /1 ) PS (Sigma US) ) ( ( PS PS. (IPGTT) ( 16 ) 1/5gr/kg [20] 0/2 0/1 (Sigma US) [20] PS (ITT) 2/5 U/kg [25] (PS ). 200 Xylazine 20 mg/kg 50 mg/kg ( 0/2 0/1 )..[16] [ ] T.[10].[3 2] [3].[4] [22] (STZ).[21] STZ..[11] Non obese diabetic mice NOD.[11] NOD NOD 20 22±

4 ± Student t test P<0/05. NOV. PS ).( 1. PS 30 / 5±3 / 1). ( 31 / 15±3 / 5 (P<0/001) 33 / 6±2 / 5) ( 13 / 9±3 / 3). ( ( ) 2 PS ( ). mmol/l -1 **.(n=10) ( ) p<0/ (Sigma US). -80 C-peptide C-peptide (Crystal chem., Chicago, US) (Linco, St. Charles, MO, US).[ ].[27]. PS 24.[15 20] 24 ) (n=10). mmol/l. ( ) ( ) -2.p<0/001 **.p<0/05. *.(

5 ) (n=10). mmol/l. ( ) ( ) -3.p<0/001 **.p<0/05. *.( /2±36/7 628/6±126/7. C peptide -4 PS C peptide.. 166/1± 26/6 27/30±12/1. C peptide 5 PS. (p<0/05) ) ) ( 0/18±0/02 0/09±0/02 28/26±5/1 15/9±2/2 120 ( 15/9±2/2) ( 4/1±0/5). (P<0/001 P<0/05) ( ) 3 ( ). 4864/4±655/ /2±1349/6 C peptide ).( PS ) (n=10). ( ) PM C peptide ( ) ug/ml -4.p<0/001 *.(student t test

6 *.(student t test ) (n=10). ( ) ( ) gr -5.p<0/05..[9 23] [22] C ) (..[4] P38 MPK [7] IL1β [26 1 7]. [21] ( 0/37±0/02 0/22 ±0/05. PS.( ) PS (P<0/001) 2/5±0/2 24 4/7±0/1 10/3±0/8 6 ) 24 14/6±0/2.( ( ).[12]. Non obese diabetic mice (NOD)

7 (.ml (.ml (.gr *.(student t test ) (n=10)..p<0/001. Prabhaker M Ebenezer IS.[18] C. [21]

8 References 13 [1] hatt S, Zalcman S, Hassanain M, Siegel. Cytokine modulation of defensive rage behavior in the cat : Role of G and interleukin-2 receptors in the medial hypothalamus. Neurosci 133 (2005) [2] Molecular and cellular characterization of the G receptor in the rat pancreas. Mol Cell Endocrinol 103 (1994) [3] raun M, Wendt, uschard K, Salehi, Sewing S, Gromada J, Rorsman P, G receptor activation inhibits exocytosis in rat pancreatic beta-cells by G- protein-dependent activation of calcineurin. J Physiol 559 (Pt 2) (2004) [4] Dong H, Kumar M, Zhang Y, Gyulkhandanyan, Xiang YY, Ye, Perrella J, Hyder, Zhang N, Wheeler M, Lu WY, Wang Q, Gamma-aminobutyric acid up- and downregulates insulin secretion from beta cells in concert with changes in glucose concentration. Diabetologia. 49 (2006) [5] Ebenezer IS, Prabhaker M, The effects of intraperitoneal administration of the G () receptor agonist baclofen on food intake in CFLP and C57L/6 mice. Eur J Pharmacol 569 (2007) 90-3 [6] Franklin IK, Wollheim C, G in the endocrine pancreas: its putative role as an islet cell paracrinesignalling molecule. J Gen Physiol 123 (2004) (3) [7] Kelley JM, Hughes L, ridges SL Jr. Does gammaaminobutyric acid (G) influence the development of chronic inflammation in rheumatoid arthritis? J Neuroinflammation 3 (2008) 5-1. [8] Kumar M, Hunag Y, Glinka Y, Prud'homme GJ, Wang Q. Gene therapy of diabetes using a novel GLP-1/IgG1- Fc fusion construct normalizes glucose levels in db/db mice. Gene Ther 14 (2007) [9] Müller, Schott-Ohly P, Dohle C, Gleichmann H. Differential regulation of Th1-type and Th2-type cytokine profiles in pancreatic islets of C57L/6 and L/c mice by multiple low doses of streptozotocin. Immunobiology 205 (2002) [10] Okada Y, Taniguchi H, Schimada C. High concentration of G and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma. Science 194 (4265) (1976) [11] Piccirillo C, Tritt M, Souroudis E, lbanese, Pyzik M, Hay V. Control of type 1 autoimmune aiabetes by naturally occurring CD4 + CD25 + regulatory T lymphocytes in neonatal NOD mice. nn N Y cad Sci 1051 (2005) [12] Prudhomme GJ, Chang Y. Prevention of autoimmune diabetes by intramuscular gene therapy with a nonviral vector encoding an interferon-gamma receptor/igg1 fusion protein. Gene Therapy 6 (1999) [13] Reetz, Solimena M, Matteoli M, Folli F, Takei K, De Camilli P. G and pancreatic beta-cells: colocalization of glutamic acid decarboxylase (GD) and G with synaptic-like microvesicles suggests their role in G storage and secretion. EMO J 10 (1991) [14] Satin LS, Kinard T. Neurotransmitters and their receptors in the islets of Langerhans of the pancreas: what messages do acetylcholine, glutamate, and G transmit? Endocrine 8 (1998) [15] Scrogin KE, Hatton DC, Chi Y, Luft FC. Chronic nitric oxide inhibition with L-NME: effects on autonomic control of the cardiovascular system. m J Physiol 274 (1998) R367-R374. [16] Shi Y, Kanaani J, Menard-Rose V, Ma YH, Chang PY, Hanahan D, et al. Increased expression of GD65 and G in pancreatic beta-cells impairs first-phase insulin secretion. m J Physiol Endocrinol Metab 279 (2000) E [17] Soltani N, Keshavarz M, Dehpour R. Effect of oral magnesium sulfate administration on blood pressure and lipid profile in streptozocin diabetic rat. Eur J Pharmacol 560 (2007) [18] Soltani N, Keshavarz M, Wang Q. Effect of G on plasma cytokine concentration and beta and alpha cell mass in CD1 diabetic mice. Ir J Endocrinol Metabolism. 10 (2008) [19] Soltani N, Keshavarz M, Wang Q. Prevention effect of G on type one diabetes in NOD mice. Ir J Diabetes lipid disorder 7 ( 2008) [20] Soltani N, Kumar M, Glinka Y, Prud'homme GJ, Wang Q. In vivo expression of GLP-1/IgG1-Fc fusion protein enhances beta-cell mass and protects against streptozotocin-induced diabetes. Gene Ther 14 (2007) [21] Soltani N, Keshavarz M, Minaii, Zahdi sl S, Dehpour

9 R, Effect of magnesium on plasma glucose and pancreas histology in streptozotocin-diabetic rats. CEPP 32 (2005) [22] Soltani N, Keshavarz M, Sohanaki H, Dehpour R, Zahdi sl S, Oral magnesium sulfate prevent vascular complication STZ-diabetic rats. Life sciences 76 (2005) [23] Sun N, Yang G, Zhao H, Savelkoul HF, n L. Multidose streptozotocin induction of diabetes in L/c mice induces a dominant oxidative macrophage and a conversion of TH1 to TH2 phenotypes during disease progression. Mediators Inflammation 31 (2005) [24] Taniguchi H, Okada Y, Seguchi H, Shimada C, Seki M, Tsutou, aba S, High concentration of gammaaminobutyric acid in pancreatic beta cells. Diabetes 28 (1979) [25] Wang Q, rubaker PL. Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice. Diabetologia 45 ( 2002) [26] Wang S, Cheng Q, Malik S, Yang, J. Interleukin 1 beta inhibits gama aminobutyric acid type (G ) receptor current culture hippocampal neurons. Pharmacol Exp Ther 292 (2004) [27] lum WF, Englaro P, Hanitsch S, Juul, Hertel NT, Müller J, Skakkebaek NE, Heiman ML, irkett M, ttanasio M, Kiess W, Rascher W, Plasma leptin levels in healthy children and adolescents: Dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J Clin Endocrinol Metab 82 (1997) [28] Xu E, Kumar M, Zhang Y, Ju W, Obata T, Zhang N, Liu S, Wendt, Deng S, Ebina Y, Wheeler M, raun M, Wang Q, Intra-islet insulin suppresses glucagon release via G-G receptor system. Cell Metab 3 (2006)