| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-cell survival through a
PI 3-kinase/Akt-signaling pathway
Divisions of 1 Gastroenterology and 2 Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110
The concentration of glucose in
plasma is an important determinant of pancreatic 
-cell mass, whereas
the relative contributions of hypertrophy, proliferation, and cell
survival to this process are unclear. Glucose results in depolarization
and subsequent calcium influx into islet -cells. Because
depolarization and calcium (Ca2+) influx promote survival
of neuronal cells, we hypothesized that glucose might alter survival of
islet -cells through a similar mechanism. In the present studies,
cultured mouse islet -cells showed a threefold decrease in
apoptosis under conditions of 15 mM glucose compared with 2 mM
glucose (P < 0.05). MIN6 insulinoma cells incubated in
25 mM glucose for 24 h showed a threefold decrease in
apoptosis compared with cells in 5 mM glucose (1.7 ± 0.2 vs. 6.3 ± 1%, respectively, P < 0.001). High
glucose (25 mM) enhanced survival-required depolarization and
Ca2+ influx and was blocked by phosphatidylinositol (PI)
3-kinase inhibitors. Glucose activation of the protein kinase Akt was
demonstrated in both insulinoma cells and cultured mouse islets by
means of an antibody specific for Ser473 phospho-Akt and by
an in vitro Akt kinase assay. Akt phosphorylation was dependent on PI
3-kinase but not on MAPK. Transfection of insulinoma cells with an Akt
kinase-dead plasmid (Akt-K179M) resulted in loss of glucose-mediated
protection, whereas transfection with a constitutively active Akt
enhanced survival in glucose-deprived insulinoma cells. The results of
these studies defined a novel pathway for glucose-mediated activation
of a PI 3-kinase/Akt survival-signaling pathway in islet -cells.
This pathway may provide important targets for therapeutic intervention.
phosphatidylinositol 3-kinase; apoptosis; islet -cell
mass; depolarization
This article has been cited by other articles:
|
|
 |
|
  A. El Ouaamari, N. Baroukh, G. A. Martens, P. Lebrun, D. Pipeleers, and E. van Obberghen miR-375 Targets 3'-Phosphoinositide-Dependent Protein Kinase-1 and Regulates Glucose-Induced Biological Responses in Pancreatic {beta}-Cells Diabetes, October 1, 2008; 57(10): 2708 - 2717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Jetton, B. Everill, J. Lausier, V. Roskens, A. Habibovic, K. LaRock, A. Gokin, M. Peshavaria, and J. L. Leahy Enhanced {beta}-cell mass without increased proliferation following chronic mild glucose infusion Am J Physiol Endocrinol Metab, April 1, 2008; 294(4): E679 - E687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Kiraly, H. E. Bates, N. A. Kaniuk, J. T. Y. Yue, J. H. Brumell, S. G. Matthews, M. C. Riddell, and M. Vranic Swim training prevents hyperglycemia in ZDF rats: mechanisms involved in the partial maintenance of {beta}-cell function Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E271 - E283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-i. Han, S. Aramata, K. Yasuda, and K. Kataoka MafA Stability in Pancreatic {beta} Cells Is Regulated by Glucose and Is Dependent on Its Constitutive Phosphorylation at Multiple Sites by Glycogen Synthase Kinase 3 Mol. Cell. Biol., October 1, 2007; 27(19): 6593 - 6605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Alonso, T. Yokoe, P. Zhang, D. K. Scott, S. K. Kim, C. P. O'Donnell, and A. Garcia-Ocana Glucose Infusion in Mice: A New Model to Induce {beta}-Cell Replication Diabetes, July 1, 2007; 56(7): 1792 - 1801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A Glauser and W. Schlegel The emerging role of FOXO transcription factors in pancreatic {beta} cells J. Endocrinol., May 1, 2007; 193(2): 195 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Yermen, A. Tomas, and P. A. Halban Pro-Survival Role of Gelsolin in Mouse {beta}-Cells Diabetes, January 1, 2007; 56(1): 80 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Fernandez, M. A. Martin, S. Fajardo, F. Escriva, and C. Alvarez Increased IRS-2 content and activation of IGF-I pathway contribute to enhance beta-cell mass in fetuses from undernourished pregnant rats Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E187 - E195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Martinez, C. Cras-Meneur, E. Bernal-Mizrachi, and M. A. Permutt Glucose Regulates Foxo1 Through Insulin Receptor Signaling in the Pancreatic Islet {beta}-cell Diabetes, June 1, 2006; 55(6): 1581 - 1591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, H. Chen, and P. N. Epstein Metallothionein and Catalase Sensitize to Diabetes in Nonobese Diabetic Mice: Reactive Oxygen Species May Have a Protective Role in Pancreatic {beta}-Cells Diabetes, June 1, 2006; 55(6): 1592 - 1604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Stiles, C. Kuralwalla-Martinez, W. Guo, C. Gregorian, Y. Wang, J. Tian, M. A. Magnuson, and H. Wu Selective Deletion of Pten in Pancreatic {beta} Cells Leads to Increased Islet Mass and Resistance to STZ-Induced Diabetes. Mol. Cell. Biol., April 1, 2006; 26(7): 2772 - 2781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Jetton, J. Lausier, K. LaRock, W. E. Trotman, B. Larmie, A. Habibovic, M. Peshavaria, and J. L. Leahy Mechanisms of Compensatory {beta}-Cell Growth in Insulin-Resistant Rats: Roles of Akt Kinase Diabetes, August 1, 2005; 54(8): 2294 - 2304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Morais, J. Westhuyzen, B. Pat, G. Gobe, and H. Healy High ambient glucose is effect neutral on cell death and proliferation in human proximal tubular epithelial cells Am J Physiol Renal Physiol, August 1, 2005; 289(2): F401 - F409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Rao, J. Roccisana, K. K. Takane, R. Bottino, A. Zhao, M. Trucco, and A. Garcia-Ocana Gene Transfer of Constitutively Active Akt Markedly Improves Human Islet Transplant Outcomes in Diabetic Severe Combined Immunodeficient Mice Diabetes, June 1, 2005; 54(6): 1664 - 1675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Srinivasan, M. Ohsugi, Z. Liu, S. Fatrai, E. Bernal-Mizrachi, and M. A. Permutt Endoplasmic Reticulum Stress-Induced Apoptosis Is Partly Mediated by Reduced Insulin Signaling Through Phosphatidylinositol 3-Kinase/Akt and Increased Glycogen Synthase Kinase-3{beta} in Mouse Insulinoma Cells Diabetes, April 1, 2005; 54(4): 968 - 975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Navarro-Tableros, M. C. Sanchez-Soto, S. Garcia, and M. Hiriart Autocrine Regulation of Single Pancreatic {beta}-Cell Survival Diabetes, August 1, 2004; 53(8): 2018 - 2023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hammar, G. Parnaud, D. Bosco, N. Perriraz, K. Maedler, M. Donath, D. G. Rouiller, and P. A. Halban Extracellular Matrix Protects Pancreatic {beta}-Cells Against Apoptosis: Role of Short- and Long-Term Signaling Pathways Diabetes, August 1, 2004; 53(8): 2034 - 2041. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
