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Adrenaline,noradrenaline inhibits insulin secretion

Stable Identifier
R-HSA-400042
Type
Pathway
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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.

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