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Abstract:
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The present work is an attempt to understand the role of acetylcholine
muscarinic M1 and M3 receptors during pancreatic regeneration and insulin
secretion. The work focuses on the changes in the muscarinic M1 and M3 receptors
in brain and pancreas during pancreatic regeneration. The effect of these receptor
subtypes on insulin secretion and pancreatic P-cell proliferation were studied in vitro
using rat primary pancreatic islet culture. Muscarinic Ml and M3 receptor kinetics
and gene expression studies during pancreatic regeneration and insulin secretion will
help to elucidate the role of acetylcholine functional regulation of pancreatic u-cell
proliferation and insulin secretion.The cholinergic system through muscarinic M1
and M3 receptors play an important role in the regulation of pancreatic (3-cell
proliferation and insulin secretion . Cholinergic activity as indicated by acetylcholine
esterase, a marker for cholinergic system, decreased in the brain regions -
hypothalamus, brain stem, corpus striatum, cerebral cortex and cerebellum during
pancreatic regeneration. Pancreatic muscarinic M1 and M3 receptor activity increased during proliferation indicating that both receptors are stimulatory to (3-cell division. Acetylcholine dose dependently increase EGF induced DNA synthesis in pancreatic islets in vitro, which is inhibited by muscarinic antagonist atropine confirming the role of muscarinic receptors. Muscarinic M1 and M3 receptor antagonists also block acetycholine induced DNA synthesis suggesting the importance of these receptors in regeneration. Acetylcholine also stimulated glucose induced insulin secretion in vitro which is inhibited by muscarinic M1 and M3 receptor antagonists. The muscarinic receptors activity and their functional balance in the brain and pancreas exert a profound influence in the insulin secretion and also regeneration of pancreas |