Jayanarayanan, S; Dr. Paulose, C S(Cochin University Of Science And Technology, December 21, 2012)
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Abstract:
The present study was designed to investigate the protective effect of
curcumin and vitamin D3 in the functional regulation of glutamatergic NMDA and
AMPA receptors in streptozotocin (STZ) induced diabetic rats. Alterations in
glutamatergic neurotransmission in the brain were evaluated by analyzing the
glutamate content, glutamate receptors - NMDA and AMPA receptors binding
parameters and gene expression, GAD and GLAST gene expression.
Immunohistochemistry studies using confocal microscope were carried out to
confirm receptor density and gene expression results of NMDA and AMPA
receptors. The role of glutamatergic receptors in pancreas was studied using the
following parameters; glutamate content, GLAST expression, glutamate receptors
- NMDA and AMPA receptor binding and gene expression. Increasing evidence in
both experimental and clinical studies suggests that oxidative stress plays a major
role in the pathogenesis of diabetes. In the present study SOD assay and GPx gene
expression were done to evaluate the activity of antioxidant enzymes in the brain
regions and pancreas. NeuroD1 and Pdx1 gene expression were performed in
pancreas of experimental rats to evaluate pancreatic islet survival. Gene
expression profiles of caspase 8, Bax, and Akt in brain regions and pancreas were
studied to understand the possible mechanism behind curcumin and vitamin D3
mediated neuroprotection and islet survival. Gene expression studies of
vitamin D3 receptor localisation in the pancreas was done to understand the
mechanism of vitamin D3 in insulin secretion. Curcumin and vitamin D3 mediated
insulin secretion via Ca2+ release were studied using confocal microscope.
Description:
Department of Biotechnology
Cochin University of Science and Technology
Anitha, M; Dr. Paulose, C S(Cochin University of Science and Technology, July , 2012)
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Abstract:
This thesis Entitled Neuronal degeneration in streptozotocin induced diabetic rats: effect of aegle marmelose and pyridoxine in pancreatic B cell proliferation and neuronal survival. Diabetes mellitus, a chronic metabolic disorder results in neurological dysfunctions and structural changes in the CNS. Antioxidant therapy is a challenging but necessary dimension in the management of diabetes and neurodegenerative changes associated with it. Our results showed regional variation and imbalance in the expression pattern of dopaminergic receptor subtypes in diabetes and its role in imbalanced insulin signaling and glucose regulation. Disrupted dopaminergic signaling and increased hyperglycemic stress in diabetes contributed to the neuronal loss. Neuronal loss in diabetic rats mediated through the expression of pattern of GLUT-3, CREB, IGF-1, Akt-1, NF,B, second messengers- cAMP, cGMP, IP3 and activation of apoptotic factors factors- TNF-a,caspase-8. Disrupted dopaminergic receptor expressions and its signaling in pancreas contributed defective insulin secretion in diabetes. Activation of apoptotic factors- TNF- a,caspase-8 and defective functioning of neuronal survival factors, disrupted second messenger signaling modulated neuronal viability in diabetes. Hyperglycemic stress activated the expression of TNF-a,caspase-8, BAX and differential expression of anti oxidant
enzymes- SOD and GPx in liver lead to apoptosis. Treatment of diabetic rats with insulin, Aegle marmelose and pyridoxine significantly reversed the altered dopaminergic neurotransmission, GLUT3, GLUT2, IGF-1 and second messenger signaling. Antihyperglycemic and antioxidant activity of Aegle marmelose and pyridoxine enhanced pancreatic B cell proliferation, increased insulin synthesis and secretion in diabetic rats. Thus our results conclude the neuroprotective and regenerating ability of Aegle marmelose and pyridoxine which in turn has a novel therapeutic role in the management of diabetes.
Description:
Center for neuroscience, Department of Biotechnology, Cochin University of Science and Technology