Dissociation of Gi/o Heterotrimeric G-protein Complex Binding of Adrenaline or Noradrenaline by Alpha-2A/2C Adrenergic Receptors Activation of Gi/o Heterotrimeric G Proteins by Alpha Adrenergic Receptors Alpha-2A/2C Closing (Inhibition) of L-type Calcium Channels in Pancreatic Beta Cells Opening of Potassium Channels in Pancreatic Beta Cells in Response to Epinephrine Inhibition of Adenylate Cyclase by G-beta:G-gamma PathwayStep2025 PathwayStep2026 PathwayStep2024 PathwayStep2023 PathwayStep2022 PathwayStep2021 Inhibition of Insulin Secretion by Adrenaline/Noradrenaline Authored: May, B, 2009-05-27 03:41:50 Edited: May, B, 2009-05-27 03:41:50 Pubmed10449730 Pubmed12684222 Pubmed14514350 Pubmed17900700 Pubmed18162464 Pubmed7641683 Pubmed8997178 Reactome Database ID Release 43400042 Reactome, http://www.reactome.org ReactomeREACT_18339 Reviewed: D'Eustachio, P, 2009-06-02 00:48:17 The catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine) inhibit insulin secretion from pancreatic beta cells. Four effects are seen in the cells:<br>1. Inhibition of exocytosis of secretory granules, the major effect.<br>2. Opening of ATP-sensitive potassium channels (KATP channels) and repolarization of the cell.<br>3. Closing of L-type voltage-dependent calcium channels and inhibition of calcium influx.<br>4. Inhibition of adenylyl cyclase activity.<br>The first event in adrenaline/noradrenaline signaling in beta cells is the binding of adrenaline or noradrenaline to alpha-2 adrenergic receptors, which are G-protein coupled receptors. Binding activates the alpha subunits in heterotrimeric Gi and Go complexes to exchange GDP for GTP, forming the active G alpha:GTP complex. Experiments using specific antibodies against the alpha subunits in mice show that Gi alpha-1, Gi alpha-2, and Go alpha-2 are responsible for adrenergic effects. The exact beta and gamma subunits of the heterotrimeric G-proteins are unknown.<br>After activation by GTP, the heterotrimeric complex dissociates into the G alpha:GTP complex and the beta:gamma complex. The G alpha:GTP complex causes the inhibition of exocytosis by an unknown mechanism that involves protein acylation. This is responsible for most of the observed inhibition of insulin secretion. Additionally, the G alpha:GTP complex activates (opens) KATP channels, allowing the cell to repolarize. The beta:gamma complex inhibits (closes) voltage-dependent calcium channels, reducing the intracellular calcium concentration, and inhibits adenylyl cyclase, reducing the intracellular cAMP concentration.