title: Striatal dopamine receptors modulate the expression of insulin receptor, IGF-1 and GLUT-3 in diabetic rats: effect of pyridoxine treatment.
abstract: The incidence of type 2 diabetes mellitus is rising at alarming proportions. Central nervous system plays an important part in orchestrating glucose metabolism, with accumulating evidence linking dysregulated central nervous system circuits to the failure of normal glucoregulatory mechanisms. Pyridoxine is a water soluble vitamin and it has important role in brain function. This study aims to evaluate the role of pyridoxine in striatal glucose regulation through dopaminergic receptor expressions in streptozotocin induced diabetic rats. Radio receptor binding assays for dopamine D(1), D(2) receptors were done using [(3)H] 7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol and [(3)H] 5-chloro-2-methoxy-4-methylamino-N-[-2-methyl-1-(phenylmethyl)pyrrolidin-3-yl]benzamide. Gene expressions were done using fluorescently labeled Taqman probes of dopamine D(1), D(2) receptor, Insulin receptor, Insulin like growth factor-1(IGF-1) and Glucose transporter-3 (GLUT-3). Bmax of dopamine D(1) receptor is decreased and B(max) of dopamine D(2) was increased in diabetic rats compared to control. Gene expression of dopamine D(1) receptor was down regulated and dopamine D(2) receptor was up regulated in diabetic rats. Our results showed decreased gene expression of Insulin receptor, IGF-1 and increased gene expression of GLUT-3 in diabetic rats compared to control. Pyridoxine treatment restored diabetes induced alterations in dopamine D(1), D(2) receptors, Insulin receptor, IGF-1, GLUT-3 gene expressions in striatum compared to diabetic rats. Insulin treatment reversed dopamine D(1), D(2) receptor, GLUT-3 mRNA expression, D(2) receptor binding parameters in the striatum compared to diabetic group. Our results suggest the potential role of pyridoxine supplementation in ameliorating diabetes mediated dysfunctions in striatal dopaminergic receptor expressions and insulin signaling. Thus pyridoxine has therapeutic significance in diabetes management.
authors.affiliation: Department of Biotechnology, Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Cochin University of Science and Technology, Cochin 682 022, Kerala, India.
authors.forename: M
authors.initials: M
authors.lastname: Anitha
authors.forename: Pretty Mary
authors.initials: PM
authors.lastname: Abraham
authors.forename: C S
authors.initials: CS
authors.lastname: Paulose
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D051274:Glucose Transporter Type 3 / Q000235:genetics; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D011736:Pyridoxine / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D051274:Glucose Transporter Type 3; D007004:Hypoglycemic Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C495690:Slc2a3 protein, rat; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D011736:Pyridoxine