The Mechanism of Autonomic Nervous System in the Regulation of Insulin Secretion

Abstract

The regulation of insulin secretion is important for the maintenance of normal glucose homeostasis. There are at least four major pathways of the stimulation of insulin secretion that have been defined. The first major pathway is high concentration of glucose which causes inhibition of ATPsensitive K⁺ (K_ATP) channel and then depolarization of the plasma membrane. The second pathway is the K_ATP channel-independent pathway of glucose action or a distal effect. The third pathway is the activation of phospholipase C-β by pertussis toxin (PTX)-insensitive G-protein, resulting in enhancement of the effect on stimulated secretion of agonists such as acetylcholine and cholecystokinin. The fourth pathway is the activation of adenyl cyclase by G_s thereby activation of protein kinase A (PKA). The activation of PKA causes a small increase of [Ca²⁺]_i and a large increase of insulin secretion. The autonomic nervous system plays both positive and negative roles in the regulation of insulin secretion from pancreatic β-cells. Acetylcholine activates muscarinic M3 receptor subtype, which is parasympathetic nervous system, then increases insulin secretion by combined effects of activation of phospholipase C- β and a distal effect independent of a rise of [Ca²⁺];. For sympathetic nervous system, activation of β₂-adrenergic receptors coupled to G_s enhances insulin secretion, whereas activation of α₂-adrenergic receptors coupled to G_i/G_o inhibits insulin secretion. The mechanisms underlying α₂-adrenergic agonists inhibit insulin secretion are activation of K_ATP channel, inhibition of Ca²⁺-channel, inhibition of adenylyl cyclase and others.