Adrenaline,noradrenaline inhibits insulin secretion

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser

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.

Literature References
PubMed ID Title Journal Year
7641683 Direct control of exocytosis by receptor-mediated activation of the heterotrimeric GTPases Gi and G(o) or by the expression of their active G alpha subunits

Okamoto, T, Regazzi, R, Kiraly, C, Lang, J, Weller, U, Wollheim, CB, Nishimoto, I

EMBO J 1995
8997178 Mechanisms of inhibition of insulin release

Sharp, GW

Am J Physiol 1996
14514350 Inhibition of insulin secretion via distinct signaling pathways in alpha2-adrenoceptor knockout mice

Chao, CM, Brede, M, Hein, L, Sieg, A, Peterhoff, M, Ullrich, S

Eur J Endocrinol 2003
10449730 Regions on adenylyl cyclase that are necessary for inhibition of activity by beta gamma and G(ialpha) subunits of heterotrimeric G proteins

Wittpoth, C, Scholich, K, Yigzaw, Y, Patel, TB, Stringfield, TM

Proc Natl Acad Sci U S A 1999
12684222 Protein acylation in the inhibition of insulin secretion by norepinephrine, somatostatin, galanin, and PGE2

Straub, SG, Sharp, GW, Cheng, H

Am J Physiol Endocrinol Metab 2003
17900700 G-protein-coupled receptors and islet function-implications for treatment of type 2 diabetes

Ahren, B, Winzell, MS

Pharmacol Ther 2007
18162464 Both G i and G o heterotrimeric G proteins are required to exert the full effect of norepinephrine on the beta-cell K ATP channel

Straub, SG, Fang, Q, Sharp, GW, Zhao, Y

J Biol Chem 2008
Event Information
Orthologous Events
Cross References
BioModels Database
Cite Us!