Remya, Robinson; Dr. Paulose, C S(Cochin University of Science and Technology, April , 2007)
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Abstract:
In the present study a detailed investigation on the alterations of dopamine
and its receptors in the brain regions of streptozotocin induced diabetic and insulin
induced hypoglycaemic rats were carried out. Glutamate receptor, NMDARI gene
expression in the hypoglycaemic and hyperglycaemic brain was also studied. EEG
recording in hypoglycaemic and hyperglycaemic will be carried out to measure brain
activity. in vitro studies on glucose uptake and insulin secretion, with and without
specific antagonists were carried out to confirm the specific receptor subtypes - DA
D1, DA D2 and NMDA involved in the functional regulation during hyperglycaemic
and hypoglycaemic brain damage. The molecular studies on the brain damage
through dopaminergic and glutamergic receptors will elucidate the therapeutic role in
the corrective measures of the damage to the brain during hypoglycaemia and
hyperglycaemia. This has importance in the management of diabetes and antidiabetic
treatment for better intellectual functioning of the individual.
Description:
Department of
Biotechnology, Cochin University of Science and Technology
Eswar Shankar,P N; Paulose,C S(DEPARTMENT OF BIOTECHNOLOGY, March , 2003)
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Abstract:
Diabetes Mellitus is a metabolic disorder associated with insulin deficiency, which not.only affects the carbohydrate metabolism but also is associated with various central and peripheral complications. Chronic hyperglycemia during diabetes mellitus is a major initiator of diabetic microvascular complications like retinopathy, neuropathy, The central nervous system (CNS) neurotransmitters play
an important role in the regulation of glucose homeostasis. These neurotransmitters mediate rapid intracellular communications not only within the central nervous system but also in the peripheral tissues. They exert their function through receptors present in both neuronal and non neuronal cell surface that trigger second messenger signaling pathways. Dopamine is a neurotransmitter that has been implicated in various central neuronal degenerative disorders like Parkinson's disease and behavioral diseases like Schizophrenia. Dopamine is synthesised from tyrosine, stored in vesicles in axon terminals and released when the neuron is depolarised. Dopamine interacts with specific membrane receptors to produce its effect. Dopamine plays an important role both centrally and peripherally. The recent identification of five dopamine receptor subtypes provides a basis for understanding dopamine's central and peripheral actions . Dopamine receptors are classified into two major groups : DA D1 like and DA D2 like. Dopamine D1 like receptors consists of DA D1 and DA D5 receptors . Dopamine D2 like receptors consists of DA D2, DA D3 and DA D4 receptors. Stimulation of the DA D1 receptor gives rise to increased production of cAMP. Dopamine D2 receptors inhibit cAMP production, but activate the inositol phosphate second messenger system . Impairment of central dopamine neurotransmission causes muscle rigidity, hormonal regulation , thought disorder and cocaine addiction. Peripheral dopamine receptors mediate changes in blood flow, glomerular filtration rate, sodium excretion and catecholamine release. The dopamine D2 receptors increased in the corpus striatum and cerebral cortex but decreased in the hypothalamus and brain stem indicating their involvement in regulating insulin secretion. Dopamine D2 receptor which has a stimulatory effecton insulin secretion decreased in the pancreatic islets during diabetes. Our in vitro studies confirmed the stimulatory role of dopamine D2 receptors in stimulation of glucose induced insulin secretion. A detailed study at the molecular level on the mechanisms involved in the role of dopamine in insulin secretion, its functional modification could lead to therapeutic interventions that will have immense clinical importance.