Receptors

Cell’s behaviours of like growth, motility, differentiation and apoptosis are regulated by signals received from their environment. These extracellular signaling molecules include neurotransmitters, hormones and growth factors which regulate the activation of intracellular signaling pathways leading to changes in gene expression and cell fate. Cholinergic system through muscarinic M1 and M3 receptors play an important role in the regulation of pancreatic b-cell proliferation and insulin secretion. Cholinergic activity was decreased in the brain regions – hypothalamus, brain stem, corpus striatum, cerebral cortex and cerebellum during pancreatic regeneration. Muscarinic M1 receptors were decreased at time of regeneration while M3 receptors showed an increase. Gene expression studies confirmed the mRNA level of M1 and M3 receptors. These changes in the muscarinic receptors regulate sympathetic activity and maintain glucose level. Pancreatic muscarinic M1 and M3 receptor activity were increased during proliferation indicating that both receptors are stimulatory to pancreatic b-cell division. Acetylcholine dose dependently increased EGF induced DNA synthesis in pancreatic islets in vitro which is inhibited by muscarinic antagonist atropine confirming the role of muscarinic receptors. Acetylcholine also stimulated glucose induced insulin secretion in vitro which is inhibited by muscarinic M1 and M3 receptor antagonists. Thus it is suggested that central muscarinic M1 and M3 receptor subtypes functional difference regulates sympathetic and parasympathetic systems which control the islet cell proliferation and glucose homeostasis.