description
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

external resources
NCBI:1270103
REACTOME:R-HSA-400042
PUBMED:12684222
PUBMED:7641683
PUBMED:8997178
PUBMED:18162464
PUBMED:10449730
PUBMED:17900700
PUBMED:14514350

genes
ADCY5 , ADCY6 , ADRA2A , ADRA2C , CACNA1C , CACNA1D , CACNB2 , CACNB3 , GNAI1 , GNAI2 , GNB1 , GNB2 , GNB3 , GNG3 , GNG4 , GNG5 , GNG7 , GNG10 , GNG11 , GNGT1 , GNGT2 , CACNA2D2 , GNB5 , GNG13 , GNG2 , GNG12 , GNB4 , GNG8 ,