Am J Physiol Cell Physiol Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 271: C1781-C1799, 1996;
0363-6143/96 $5.00
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sharp, G. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharp, G. W.

AJP - Cell Physiology, Vol 271, Issue 6 C1781-C1799, Copyright © 1996 by American Physiological Society

ARTICLES

Mechanisms of inhibition of insulin release

G. W. Sharp
Department of Pharmacology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.

Several agonists including norepinephrine, somatostatin, galanin, and prostaglandins inhibit insulin release. The inhibition is sensitive to pertussis toxin, indicating the involvement of heterotrimeric Gi and/or Go proteins. Receptors for the different agonists have different selectivity for these G proteins. After G protein activation, the alpha- and beta gamma-subunits dissociate and interact with multiple targets to inhibit release. These include 1) the ATP-sensitive K+ channel and perhaps other K+ channels, 2) L-type voltage-dependent Ca2+ channels, 3) adenylyl cyclase, and 4) a "distal" site late in stimulus-secretion coupling. The latter effect, which may be exerted close to the final stage of exocytosis, is the most powerful of the individual inhibitory mechanisms. G protein action on the target molecules is determined by the individual G proteins activated and their specificity for the targets. The L-type Ca2+ channel is inhibited by G(o)-1. Adenylyl cyclase is inhibited by Gi-2 and Gi-3. The distal inhibition can be exerted by Gi-1, Gi-2, Gi-3, and G(o)-2. Thus there is both selectivity and promiscuity in G protein action in the beta-cell. These characteristics allow an inhibitory ligand to be effective at multiple targets and to act differentially from other inhibitory ligands.


This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
P. Mitrani, M. Srinivasan, C. Dodds, and M. S. Patel
Autonomic involvement in the permanent metabolic programming of hyperinsulinemia in the high-carbohydrate rat model
Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1364 - E1377.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
P. Mitrani, M. Srinivasan, C. Dodds, and M. S. Patel
Role of the autonomic nervous system in the development of hyperinsulinemia by high-carbohydrate formula feeding to neonatal rats
Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1069 - E1078.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
H. Cheng, S. G. Straub, and G. W. G. Sharp
Inhibitory role of Src family tyrosine kinases on Ca2+-dependent insulin release
Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E845 - E852.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
S. Seino and T. Shibasaki
PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis
Physiol Rev, October 1, 2005; 85(4): 1303 - 1342.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. Sieg, J. Su, A. Munoz, M. Buchenau, M. Nakazaki, L. Aguilar-Bryan, J. Bryan, and S. Ullrich
Epinephrine-induced hyperpolarization of islet cells without KATP channels
Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E463 - E471.
[Abstract] [Full Text]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
H. Cheng, S. G. Straub, and G. W. G. Sharp
Protein acylation in the inhibition of insulin secretion by norepinephrine, somatostatin, galanin, and PGE2
Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E287 - E294.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
M. Srinivasan, S. G. Laychock, D. J. Hill, and M. S. Patel
Neonatal Nutrition: Metabolic Programming of Pancreatic Islets and Obesity
Experimental Biology and Medicine, January 1, 2003; 228(1): 15 - 23.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
R. Amin, H.-Q. Chen, M. Tannous, R. Gibbs, and A. Kowluru
Inhibition of Glucose- and Calcium-Induced Insulin Secretion from beta TC3 Cells by Novel Inhibitors of Protein Isoprenylation
J. Pharmacol. Exp. Ther., October 1, 2002; 303(1): 82 - 88.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
C. B. Wollheim and P. Maechler
{beta}-Cell Mitochondria and Insulin Secretion: Messenger Role of Nucleotides and Metabolites
Diabetes, February 1, 2002; 51(90001): S37 - 42.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
T. K. Bratanova-Tochkova, H. Cheng, S. Daniel, S. Gunawardana, Y.-J. Liu, J. Mulvaney-Musa, T. Schermerhorn, S. G. Straub, H. Yajima, and G. W.G. Sharp
Triggering and Augmentation Mechanisms, Granule Pools, and Biphasic Insulin Secretion
Diabetes, February 1, 2002; 51(90001): S83 - 90.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
R. Aalinkeel, M. Srinivasan, F. Song, and M. S. Patel
Programming into adulthood of islet adaptations induced by early nutritional intervention in the rat
Am J Physiol Endocrinol Metab, September 1, 2001; 281(3): E640 - E648.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
F. Song, M. Srinivasan, R. Aalinkeel, and M. S. Patel
Use of a cDNA Array for the Identification of Genes Induced in Islets of Suckling Rats by a High-Carbohydrate Nutritional Intervention
Diabetes, September 1, 2001; 50(9): 2053 - 2060.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
M. Srinivasan, R. Aalinkeel, F. Song, B. Lee, S. G. Laychock, and M. S. Patel
Adaptive changes in insulin secretion by islets from neonatal rats raised on a high-carbohydrate formula
Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1347 - E1357.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Y. Anouar, H.-W. Lee, and L. E. Eiden
Both Inducible and Constitutive Activator Protein-1-Like Transcription Factors Are Used for Transcriptional Activation of the Galanin Gene by Different First and Second Messenger Pathways
Mol. Pharmacol., July 1, 1999; 56(1): 162 - 169.
[Abstract] [Full Text]

Home page
 Proc. Natl. Acad. Sci. USAHome page
N. Takahashi, T. Kadowaki, Y. Yazaki, G. C. R. Ellis-Davies, Y. Miyashita, and H. Kasai
Post-priming actions of ATP on Ca2+-dependent exocytosis in pancreatic beta cells
PNAS, January 19, 1999; 96(2): 760 - 765.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Filipsson, S. Karlsson, and B. Ahren
Evidence for Contribution by Increased Cytoplasmic Na+ to the Insulinotropic Action of PACAP38 in HIT-T15 Cells
J. Biol. Chem., December 4, 1998; 273(49): 32602 - 32607.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
J. A. Love, N. W. Richards, C. Owyang, and D. C. Dawson
Muscarinic modulation of voltage-dependent Ca2+ channels in insulin-secreting HIT-T15 cells
Am J Physiol Gastrointest Liver Physiol, February 1, 1998; 274(2): G397 - G405.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Roduit, J. Morin, F. Masse, L. Segall, E. Roche, C. B. Newgard, F. Assimacopoulos-Jeannet, and M. Prentki
Glucose Down-regulates the Expression of the Peroxisome Proliferator-activated Receptor-alpha Gene in the Pancreatic beta -Cell
J. Biol. Chem., November 10, 2000; 275(46): 35799 - 35806.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online