JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
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
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xu, G. G.
Right arrow Articles by Wolf, B. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xu, G. G.
Right arrow Articles by Wolf, B. A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

J Biol Chem, Vol. 274, Issue 25, 18067-18074, June 18, 1999

Insulin Receptor Substrate 1-induced Inhibition of Endoplasmic Reticulum Ca2+ Uptake in beta -Cells
AUTOCRINE REGULATION OF INTRACELLULAR Ca2+ HOMEOSTASIS AND INSULIN SECRETION

Gang G. Xu, Zhi-yong Gao, Prabhakar D. Borge Jr., and Bryan A. Wolf

From the Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

To understand the role of the insulin receptor pathway in beta -cell function, we have generated stable beta -cells (beta IRS1-A) that overexpress by 2-fold the insulin receptor substrate-1 (IRS-1) and compared them to vector-expressing controls. IRS-1 overexpression dramatically increased basal cytosolic Ca2+ levels from 81 to 278 nM, but it did not affect Ca2+ response to glucose. Overexpression of the insulin receptor also caused an increase in cytosolic Ca2+. Increased cytosolic Ca2+ was due to inhibition of Ca2+ uptake by the endoplasmic reticulum, because endoplasmic reticulum Ca2+ uptake and content were reduced in beta IRS1-A cells. Fractional insulin secretion was significantly increased 2-fold, and there was a decrease in beta IRS1-A insulin content and insulin biosynthesis. Steady-state insulin mRNA levels and glucose-stimulated ATP were unchanged. High IRS-1 levels also reduced beta -cell proliferation. These data demonstrate a direct link between the insulin receptor signaling pathway and the Ca2+-dependent pathways regulating insulin secretion of beta -cells. We postulate that during regulated insulin secretion, released insulin binds the beta -cell insulin receptor and activates IRS-1, thus further increasing cytosolic Ca2+ by reducing Ca2+ uptake. We suggest the existence of a novel pathway of autocrine regulation of intracellular Ca2+ homeostasis and insulin secretion in the beta -cell of the endocrine pancreas.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
R. N. Kulkarni, M. G. Roper, G. Dahlgren, D. Q. Shih, L. M. Kauri, J. L. Peters, M. Stoffel, and R. T. Kennedy
Islet Secretory Defect in Insulin Receptor Substrate 1 Null Mice Is Linked With Reduced Calcium Signaling and Expression of Sarco(endo)plasmic Reticulum Ca2+-ATPase (SERCA)-2b and -3
Diabetes, June 1, 2004; 53(6): 1517 - 1525.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
M. I. Borelli, F. Francini, and J. J. Gagliardino
Autocrine regulation of glucose metabolism in pancreatic islets
Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E111 - E115.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
Z. Gao, R. A. Young, G. Li, H. Najafi, C. Buettger, S. S. Sukumvanich, R. K. Wong, B. A. Wolf, and F. M. Matschinsky
Distinguishing Features of Leucine and {alpha}-Ketoisocaproate Sensing in Pancreatic {beta}-Cells
Endocrinology, May 1, 2003; 144(5): 1949 - 1957.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
I. Briaud, M. K. Lingohr, L. M. Dickson, C. E. Wrede, and C. J. Rhodes
Differential Activation Mechanisms of Erk-1/2 and p70S6K by Glucose in Pancreatic {beta}-Cells
Diabetes, April 1, 2003; 52(4): 974 - 983.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. D. Borge Jr. and B. A. Wolf
Insulin Receptor Substrate 1 Regulation of Sarco-endoplasmic Reticulum Calcium ATPase 3 in Insulin-secreting beta -Cells
J. Biol. Chem., March 21, 2003; 278(13): 11359 - 11368.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. J. Barker, I. B. Leibiger, B. Leibiger, and P.-O. Berggren
Phosphorylated inositol compounds in beta -cell stimulus-response coupling
Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1113 - E1122.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
P. D. Borge, J. Moibi, S. R. Greene, M. Trucco, R. A. Young, Z. Gao, and B. A. Wolf
Insulin Receptor Signaling and Sarco/Endoplasmic Reticulum Calcium ATPase in {beta}-Cells
Diabetes, December 1, 2002; 51(90003): S427 - 433.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
F. Galbiati, L. Polastri, S. Gregori, M. Freschi, M. Casorati, U. Cavallaro, P. Fiorina, F. Bertuzzi, A. Zerbi, G. Pozza, et al.
Antitumorigenic and Antiinsulinogenic Effects of Calcitriol on Insulinoma Cells and Solid {beta}-Cell Tumors
Endocrinology, October 1, 2002; 143(10): 4018 - 4030.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Physiol.Home page
P.B. Goforth, R. Bertram, F.A. Khan, M. Zhang, A. Sherman, and L.S. Satin
Calcium-activated K+ Channels of Mouse {beta}-cells are Controlled by Both Store and Cytoplasmic Ca2+: Experimental and Theoretical Studies
J. Gen. Physiol., August 26, 2002; 120(3): 307 - 322.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Sano, S. C. H. Liu, W. S. Lane, J. E. Piletz, and G. E. Lienhard
Insulin Receptor Substrate 4 Associates with the Protein IRAS
J. Biol. Chem., May 24, 2002; 277(22): 19439 - 19447.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. G. Roper, W.-j. Qian, B. B. Zhang, R. N. Kulkarni, C. R. Kahn, and R. T. Kennedy
Effect of the Insulin Mimetic L-783,281 on Intracellular [Ca2+] and Insulin Secretion From Pancreatic {beta}-Cells
Diabetes, February 1, 2002; 51(90001): S43 - 49.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. Westerlund, B. A. Wolf, and P. Bergsten
Glucose-Dependent Promotion of Insulin Release From Mouse Pancreatic Islets by the Insulin-Mimetic Compound L-783,281
Diabetes, February 1, 2002; 51(90001): S50 - 52.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. Varadi and G. A. Rutter
Dynamic Imaging of Endoplasmic Reticulum Ca2+ Concentration in Insulin-Secreting MIN6 Cells Using Recombinant Targeted Cameleons: Roles of Sarco(endo)plasmic Reticulum Ca2+-ATPase (SERCA)-2 and Ryanodine Receptors
Diabetes, February 1, 2002; 51(90001): S190 - 201.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
K. Lange
Role of microvillar cell surfaces in the regulation of glucose uptake and organization of energy metabolism
Am J Physiol Cell Physiol, January 1, 2002; 282(1): C1 - C26.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Gao, J. Reavey-Cantwell, R. A. Young, P. Jegier, and B. A. Wolf
Synaptotagmin III/VII Isoforms Mediate Ca2+-induced Insulin Secretion in Pancreatic Islet beta -Cells
J. Biol. Chem., November 10, 2000; 275(46): 36079 - 36085.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Ma, S. Ramanadham, M. Wohltmann, A. Bohrer, F.-F. Hsu, and J. Turk
Studies of Insulin Secretory Responses and of Arachidonic Acid Incorporation into Phospholipids of Stably Transfected Insulinoma Cells That Overexpress Group VIA Phospholipase A2 (iPLA2beta ) Indicate a Signaling Rather Than a Housekeeping Role for iPLA2beta
J. Biol. Chem., April 13, 2001; 276(16): 13198 - 13208.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. A. Aspinwall, W.-J. Qian, M. G. Roper, R. N. Kulkarni, C. R. Kahn, and R. T. Kennedy
Roles of Insulin Receptor Substrate-1, Phosphatidylinositol 3-Kinase, and Release of Intracellular Ca2+ Stores in Insulin-stimulated Insulin Secretion in beta -Cells
J. Biol. Chem., July 14, 2000; 275(29): 22331 - 22338.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.