The catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine) inhibit insulin secretion from pancreatic beta cells. Four effects are seen in the cells:1. Inhibition of exocytosis of secretory granules, the major effect.2. Opening of ATP-sensitive potassium channels (KATP channels) and repolarization of the cell.3. Closing of L-type voltage-dependent calcium channels and inhibition of calcium influx.4. Inhibition of adenylyl cyclase activity.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.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.
Okamoto, T, Regazzi, R, Kiraly, C, Lang, J, Weller, U, Wollheim, CB, Nishimoto, I
Sharp, GW
Chao, CM, Brede, M, Hein, L, Sieg, A, Peterhoff, M, Ullrich, S
Wittpoth, C, Scholich, K, Yigzaw, Y, Patel, TB, Stringfield, TM
Straub, SG, Sharp, GW, Cheng, H
Ahren, B, Winzell, MS
Straub, SG, Fang, Q, Sharp, GW, Zhao, Y
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