| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Endocrine Research (Y.S., S.I.T.), Infectious Diseases (S.-L.T.), Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285; and Department of Biochemistry and McGill Cancer Center (N.S.), McGill University, Montréal, Quebéc H3G 1Y6, Canada
Correspondence: Address all correspondence and requests for reprints to: Dr. Nahum Sonenberg, Department of Biochemistry, McGill University, McIntyre Medical Services Building, 3655 Drummond Street, Room 807, Montréal, Quebéc H3G 1Y6, Canada. E-mail: nsonen{at}med.mcgill.ca; or to Dr. Yuguang Shi, Endocrine Research DC 0545, Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, Indiana 46033. E-mail: shi_yuguang{at}lilly.com
Type 2 diabetes is a polygenic disorder characterized by multiple biochemical defects including transcriptional, translational, and posttranslational abnormalities. Although major progress has been made in elucidation of factors at the transcriptional and posttranslational levels, defects at the translational level remain elusive. Mutation of a kinase that regulates translation initiation has been implicated in the etiology of a monogenic form of diabetes known as Wolcott-Rallison syndrome. Characterization of mice rendered deficient in eukaryotic initiation factors has provided model systems to study the involvement of translation in regulating insulin synthesis and secretion, hepatic function, peripheral insulin resistance, and diabetic complications. Recent progress in the understanding of endoplasmic reticulum overload by unfolded proteins has begun to uncover mechanisms leading to pancreatic ß-cell exhaustion. Future advances in this area may lead to identification of the missing links in the pathogenesis of ß-cell failures due to conditions such as hyperinsulinemia, hyperglycemia, and long-term treatment with sulfonylureas, and thus may identify novel therapeutic targets for diabetes.
This article has been cited by other articles:
 |
|
 |
|
  P. A. Zalloua, S. T. Azar, M. Delepine, N. J. Makhoul, H. Blanc, M. Sanyoura, A. Lavergne, K. Stankov, A. Lemainque, P. Baz, et al. WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon Hum. Mol. Genet., December 15, 2008; 17(24): 4012 - 4021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Raven, D. Baltzis, S. Wang, Z. Mounir, A. I. Papadakis, H. Q. Gao, and A. E. Koromilas PKR and PKR-like Endoplasmic Reticulum Kinase Induce the Proteasome-dependent Degradation of Cyclin D1 via a Mechanism Requiring Eukaryotic Initiation Factor 2{alpha} Phosphorylation J. Biol. Chem., February 8, 2008; 283(6): 3097 - 3108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yamada, H. Ishihara, A. Tamura, R. Takahashi, S. Yamaguchi, D. Takei, A. Tokita, C. Satake, F. Tashiro, H. Katagiri, et al. WFS1-deficiency increases endoplasmic reticulum stress, impairs cell cycle progression and triggers the apoptotic pathway specifically in pancreatic {beta}-cells Hum. Mol. Genet., May 15, 2006; 15(10): 1600 - 1609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cheyssac, C. Dina, F. Lepretre, V. Vasseur-Delannoy, A. Dechaume, S. Lobbens, B. Balkau, J. Ruiz, G. Charpentier, F. Pattou, et al. EIF4A2 Is a Positional Candidate Gene at the 3q27 Locus Linked to Type 2 Diabetes in French Families. Diabetes, April 1, 2006; 55(4): 1171 - 1176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Wang, Y. Wei, D. Schmoll, K. N. Maclean, and M. J. Pagliassotti Endoplasmic Reticulum Stress Increases Glucose-6-Phosphatase and Glucose Cycling in Liver Cells Endocrinology, January 1, 2006; 147(1): 350 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Hotamisligil Role of Endoplasmic Reticulum Stress and c-Jun NH2-Terminal Kinase Pathways in Inflammation and Origin of Obesity and Diabetes Diabetes, December 1, 2005; 54(suppl_2): S73 - S78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Teutonico, P. F. Schena, and S. Di Paolo Glucose Metabolism in Renal Transplant Recipients: Effect of Calcineurin Inhibitor Withdrawal and Conversion to Sirolimus J. Am. Soc. Nephrol., October 1, 2005; 16(10): 3128 - 3135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Timchenko, G.-L. Wang, and L. T. Timchenko RNA CUG-binding Protein 1 Increases Translation of 20-kDa Isoform of CCAAT/Enhancer-binding Protein {beta} by Interacting with the {alpha} and {beta} Subunits of Eukaryotic Initiation Translation Factor 2 J. Biol. Chem., May 27, 2005; 280(21): 20549 - 20557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. P. Ciaraldi, S. Mudaliar, A. Barzin, J. A. Macievic, S. V. Edelman, K. S. Park, and R. R. Henry Skeletal Muscle GLUT1 Transporter Protein Expression and Basal Leg Glucose Uptake Are Reduced in Type 2 Diabetes J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 352 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Hung, I.-J. Su, H.-Y. Lei, H.-C. Wang, W.-C. Lin, W.-T. Chang, W. Huang, W.-C. Chang, Y.-S. Chang, C.-C. Chen, et al. Endoplasmic Reticulum Stress Stimulates the Expression of Cyclooxygenase-2 through Activation of NF-{kappa}B and pp38 Mitogen-activated Protein Kinase J. Biol. Chem., November 5, 2004; 279(45): 46384 - 46392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Ozcan, Q. Cao, E. Yilmaz, A.-H. Lee, N. N. Iwakoshi, E. Ozdelen, G. Tuncman, C. Gorgun, L. H. Glimcher, and G. S. Hotamisligil Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes Science, October 15, 2004; 306(5695): 457 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Julien, J. Laine, and J. Morisset Regulation of Rat Pancreatic CCKB Receptor and Somatostatin Expression by Insulin Diabetes, June 1, 2004; 53(6): 1526 - 1534. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
