Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Type 2 Diabetes-a Matter of ß-Cell Life and Death?
Christopher J. Rhodes
Abstract:
In type 2 diabetes, the ß cells of the pancreas failto produce enough insulin to meet the body's demand, in partbecause of an acquired decrease in ß-cell mass. Inadults, pancreatic ß-cell mass is controlled by severalmechanisms, including ß-cell replication, neogenesis,hypertrophy, and survival. Here, I discuss evidence supportingthe notion that increased ß-cell apoptosis is an importantfactor contributing to ß-cell loss and the onset oftype 2 diabetes. Interestingly, a key signaling molecule thatpromotes ß-cell growth and survival, insulin receptorsubstrate 2 (IRS-2), is a member of a family of proteins whoseinhibition contributes to the development of insulin resistancein the liver and other insulin-responsive tissues. Thus, theIRS-2 pathway appears to be a crucial participant in the tenuousbalance between effective pancreatic ß-cell mass andinsulin resistance.
The Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, USA, and Department of Pharmacology, University of Washington, Seattle, WA 98122, USA.
E-mail: cjr{at}pnri.org
The editors suggest the following Related Resources on Science sites:
In Science Magazine
INTRODUCTION TO SPECIAL ISSUE
Paula A. Kiberstis (21 January 2005) Science307 (5708), 369.
[DOI: 10.1126/science.307.5708.369] |Summary »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Involvement of the Ca2+-responsive transactivator in high glucose-induced {beta}-cell apoptosis.
X. Men, L. Peng, H. Wang, W. Zhang, S. Xu, Q. Fang, H. Liu, W. Yang, and J. Lou (2013)
J. Endocrinol.
216, 231-243
|Abstract »|Full Text »|PDF »
Molecular Mechanisms That Differentiate Apoptosis from Programmed Necrosis.
Ciliary Neurotrophic Factor Protects Mice Against Streptozotocin-induced Type 1 Diabetes through SOCS3: THE ROLE OF STAT1/STAT3 RATIO IN {beta}-CELL DEATH.
L. F. Rezende, G. J. Santos, E. M. Carneiro, and A. C. Boschero (2012)
J. Biol. Chem.
287, 41628-41639
|Abstract »|Full Text »|PDF »
Vascular Endothelial Growth Factor-Mediated Islet Hypervascularization and Inflammation Contribute to Progressive Reduction of {beta}-Cell Mass.
J. Agudo, E. Ayuso, V. Jimenez, A. Casellas, C. Mallol, A. Salavert, S. Tafuro, M. Obach, A. Ruzo, M. Moya, et al. (2012)
Diabetes
61, 2851-2861
|Abstract »|Full Text »|PDF »
Formation of a Human {beta}-Cell Population within Pancreatic Islets Is Set Early in Life.
B. E. Gregg, P. C. Moore, D. Demozay, B. A. Hall, M. Li, A. Husain, A. J. Wright, M. A. Atkinson, and C. J. Rhodes (2012)
J. Clin. Endocrinol. Metab.
97, 3197-3206
|Abstract »|Full Text »|PDF »
DPP4 inhibitor vildagliptin preserves {beta}-cell mass through amelioration of endoplasmic reticulum stress in C/EBPB transgenic mice.
S. Shimizu, T. Hosooka, T. Matsuda, S.-i. Asahara, M. Koyanagi-Kimura, A. Kanno, A. Bartolome, H. Etoh, M. Fuchita, K. Teruyama, et al. (2012)
J. Mol. Endocrinol.
49, 125-135
|Abstract »|Full Text »|PDF »
Mechanisms of Cell Death in Heart Disease.
K. Konstantinidis, R. S. Whelan, and R. N. Kitsis (2012)
Arterioscler Thromb Vasc Biol
32, 1552-1562
|Abstract »|Full Text »|PDF »
Impaired {beta}-cell-{beta}-cell coupling mediated by Cx36 gap junctions in prediabetic mice.
C. P. F. Carvalho, R. B. Oliveira, A. Britan, J. C. Santos-Silva, A. C. Boschero, P. Meda, and C. B. Collares-Buzato (2012)
Am J Physiol Endocrinol Metab
303, E144-E151
|Abstract »|Full Text »|PDF »
FTY720 Normalizes Hyperglycemia by Stimulating {beta}-Cell in Vivo Regeneration in db/db Mice through Regulation of Cyclin D3 and p57KIP2.
Z. Zhao, J. Choi, C. Zhao, and Z. A. Ma (2012)
J. Biol. Chem.
287, 5562-5573
|Abstract »|Full Text »|PDF »
Glucose-Mediated Repression of Menin Promotes Pancreatic {beta}-Cell Proliferation.
H. Zhang, W. Li, Q. Wang, X. Wang, F. Li, C. Zhang, L. Wu, H. Long, Y. Liu, X. Li, et al. (2012)
Endocrinology
153, 602-611
|Abstract »|Full Text »|PDF »
Signaling Cross Talk between Growth Hormone (GH) and Insulin-Like Growth Factor-I (IGF-I) in Pancreatic Islet {beta}-Cells.
F. Ma, Z. Wei, C. Shi, Y. Gan, J. Lu, S. J. Frank, J. Balducci, and Y. Huang (2011)
Mol. Endocrinol.
25, 2119-2133
|Abstract »|Full Text »|PDF »
Bombesin Receptor Subtype-3 (BRS-3) Regulates Glucose-Stimulated Insulin Secretion in Pancreatic Islets across Multiple Species.
Y. Feng, X.-M. Guan, J. Li, J. M. Metzger, Y. Zhu, K. Juhl, B. B. Zhang, N. A. Thornberry, M. L. Reitman, and Y.-P. Zhou (2011)
Endocrinology
152, 4106-4115
|Abstract »|Full Text »|PDF »
Effects of Long-Term Cranberry Supplementation on Endocrine Pancreas in Aging Rats.
M. Zhu, J. Hu, E. Perez, D. Phillips, W. Kim, R. Ghaedian, J. K. Napora, and S. Zou (2011)
J Gerontol A Biol Sci Med Sci
66A, 1139-1151
|Abstract »|Full Text »|PDF »
FoxO Feedback Control of Basal IRS-2 Expression in Pancreatic {beta}-Cells Is Distinct From That in Hepatocytes.
S. Tsunekawa, D. Demozay, I. Briaud, J. McCuaig, D. Accili, R. Stein, and C. J. Rhodes (2011)
Diabetes
60, 2883-2891
|Abstract »|Full Text »|PDF »
Specific Glucose-Induced Control of Insulin Receptor Substrate-2 Expression Is Mediated via Ca2+-Dependent Calcineurin/NFAT Signaling in Primary Pancreatic Islet {beta}-Cells.
D. Demozay, S. Tsunekawa, I. Briaud, R. Shah, and C. J. Rhodes (2011)
Diabetes
60, 2892-2902
|Abstract »|Full Text »|PDF »
Mechanism of Amylin Fibrillization Enhancement by Heparin.
S. Jha, S. M. Patil, J. Gibson, C. E. Nelson, N. N. Alder, and A. T. Alexandrescu (2011)
J. Biol. Chem.
286, 22894-22904
|Abstract »|Full Text »|PDF »
Wolfram syndrome 1 gene (WFS1) product localizes to secretory granules and determines granule acidification in pancreatic {beta}-cells.
M. Hatanaka, K. Tanabe, A. Yanai, Y. Ohta, M. Kondo, M. Akiyama, K. Shinoda, Y. Oka, and Y. Tanizawa (2011)
Hum. Mol. Genet.
20, 1274-1284
|Abstract »|Full Text »|PDF »
{Delta}40 Isoform of p53 Controls {beta}-Cell Proliferation and Glucose Homeostasis in Mice.
C. Hinault, D. Kawamori, C. W. Liew, B. Maier, J. Hu, S. R. Keller, R. G. Mirmira, H. Scrable, and R. N. Kulkarni (2011)
Diabetes
60, 1210-1222
|Abstract »|Full Text »|PDF »
Pancreatic islet-specific overexpression of Reg3{beta} protein induced the expression of pro-islet genes and protected the mice against streptozotocin-induced diabetes mellitus.
X. Xiong, X. Wang, B. Li, S. Chowdhury, Y. Lu, C. B. Srikant, G. Ning, and J.-L. Liu (2011)
Am J Physiol Endocrinol Metab
300, E669-E680
|Abstract »|Full Text »|PDF »
Rictor/mTORC2 Is Essential for Maintaining a Balance Between {beta}-Cell Proliferation and Cell Size.
Y. Gu, J. Lindner, A. Kumar, W. Yuan, and M. A. Magnuson (2011)
Diabetes
60, 827-837
|Abstract »|Full Text »|PDF »
Erythropoietin protects against diabetes through direct effects on pancreatic {beta} cells.
D. Choi, S. A. Schroer, S. Y. Lu, L. Wang, X. Wu, Y. Liu, Y. Zhang, H. Y. Gaisano, K.-U. Wagner, H. Wu, et al. (2010)
J. Exp. Med.
207, 2831-2842
|Abstract »|Full Text »|PDF »
Deletion of Pten in Pancreatic {beta}-Cells Protects Against Deficient {beta}-Cell Mass and Function in Mouse Models of Type 2 Diabetes.
L. Wang, Y. Liu, S. Yan Lu, K.-T. T. Nguyen, S. A. Schroer, A. Suzuki, T. W. Mak, H. Gaisano, and M. Woo (2010)
Diabetes
59, 3117-3126
|Abstract »|Full Text »|PDF »
Targeting {beta}-Cell Function Early in the Course of Therapy for Type 2 Diabetes Mellitus.
J. L. Leahy, I. B. Hirsch, K. A. Peterson, and D. Schneider (2010)
J. Clin. Endocrinol. Metab.
95, 4206-4216
|Abstract »|Full Text »|PDF »
Elimination of Negative Feedback Control Mechanisms Along the Insulin Signaling Pathway Improves {beta}-Cell Function Under Stress.
D. Gurevitch, S. Boura-Halfon, R. Isaac, G. Shahaf, M. Alberstein, D. Ronen, E. C. Lewis, and Y. Zick (2010)
Diabetes
59, 2188-2197
|Abstract »|Full Text »|PDF »
Long-Term Consequences of Fetal and Neonatal Nicotine Exposure: A Critical Review.
J. E. Bruin, H. C. Gerstein, and A. C. Holloway (2010)
Toxicol. Sci.
116, 364-374
|Abstract »|Full Text »|PDF »
The Roles of ATF3, an Adaptive-Response Gene, in High-Fat-Diet-Induced Diabetes and Pancreatic {beta}-Cell Dysfunction.
E. J. Zmuda, L. Qi, M. X. Zhu, R. G. Mirmira, M. R. Montminy, and T. Hai (2010)
Mol. Endocrinol.
24, 1423-1433
|Abstract »|Full Text »|PDF »
Regulation of MafA Expression in Pancreatic {beta}-Cells in db/db Mice With Diabetes.
T.-a. Matsuoka, H. Kaneto, T. Miyatsuka, T. Yamamoto, K. Yamamoto, K. Kato, I. Shimomura, R. Stein, and M. Matsuhisa (2010)
Diabetes
59, 1709-1720
|Abstract »|Full Text »|PDF »
Targeting cyclophilin D and the mitochondrial permeability transition enhances {beta}-cell survival and prevents diabetes in Pdx1 deficiency.
K. Fujimoto, Y. Chen, K. S. Polonsky, and G. W. Dorn II (2010)
PNAS
107, 10214-10219
|Abstract »|Full Text »|PDF »
{beta}-Cell Mass Dynamics and Islet Cell Plasticity in Human Type 2 Diabetes.
S. C. Hanley, E. Austin, B. Assouline-Thomas, J. Kapeluto, J. Blaichman, M. Moosavi, M. Petropavlovskaia, and L. Rosenberg (2010)
Endocrinology
151, 1462-1472
|Abstract »|Full Text »|PDF »
Executioners of apoptosis in pancreatic {beta}-cells: not just for cell death.
{beta}-cell development and turnover during prenatal life in humans.
J. J Meier, C. U Kohler, B. Alkhatib, C. Sergi, T. Junker, H. H Klein, W. E Schmidt, and H. Fritsch (2010)
Eur. J. Endocrinol.
162, 559-568
|Abstract »|Full Text »|PDF »
Glucose Induces Pancreatic Islet Cell Apoptosis That Requires the BH3-Only Proteins Bim and Puma and Multi-BH Domain Protein Bax.
M. D. McKenzie, E. Jamieson, E. S. Jansen, C. L. Scott, D. C.S. Huang, P. Bouillet, J. Allison, T. W.H. Kay, A. Strasser, and H. E. Thomas (2010)
Diabetes
59, 644-652
|Abstract »|Full Text »|PDF »
Lack of TXNIP Protects Against Mitochondria-Mediated Apoptosis but Not Against Fatty Acid-Induced ER Stress-Mediated {beta}-Cell Death.
J. Chen, G. Fontes, G. Saxena, V. Poitout, and A. Shalev (2010)
Diabetes
59, 440-447
|Abstract »|Full Text »|PDF »
Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity.
V. B. Ritov, E. V. Menshikova, K. Azuma, R. Wood, F. G. S. Toledo, B. H. Goodpaster, N. B. Ruderman, and D. E. Kelley (2010)
Am J Physiol Endocrinol Metab
298, E49-E58
|Abstract »|Full Text »|PDF »
Islet Inflammation Impairs the Pancreatic {beta}-Cell in Type 2 Diabetes.
M. Y. Donath, M. Boni-Schnetzler, H. Ellingsgaard, and J. A. Ehses (2009)
Physiology
24, 325-331
|Abstract »|Full Text »|PDF »
Expression of the NH2-Terminal Fragment of RasGAP in Pancreatic {beta}-Cells Increases Their Resistance to Stresses and Protects Mice From Diabetes.
J.-Y. Yang, J. Walicki, E. Jaccard, G. Dubuis, N. Bulat, J.-P. Hornung, B. Thorens, and C. Widmann (2009)
Diabetes
58, 2596-2606
|Abstract »|Full Text »|PDF »
Suppression of p38 MAPK and JNK via Akt-mediated Inhibition of Apoptosis Signal-regulating Kinase 1 Constitutes a Core Component of the {beta}-Cell Pro-survival Effects of Glucose-dependent Insulinotropic Polypeptide.
S. B. Widenmaier, Z. Ao, S.-J. Kim, G. Warnock, and C. H. S. McIntosh (2009)
J. Biol. Chem.
284, 30372-30382
|Abstract »|Full Text »|PDF »
Inhibition of Nuclear Factor-{kappa}B or Bax Prevents Endoplasmic Reticulum Stress- But Not Nitric Oxide-Mediated Apoptosis in INS-1E Cells.
M. F. Tonnesen, L. G. Grunnet, J. Friberg, A. K. Cardozo, N. Billestrup, D. L. Eizirik, J. Storling, and T. Mandrup-Poulsen (2009)
Endocrinology
150, 4094-4103
|Abstract »|Full Text »|PDF »
Glucose-stimulated Expression of Txnip Is Mediated by Carbohydrate Response Element-binding Protein, p300, and Histone H4 Acetylation in Pancreatic Beta Cells.
H. Cha-Molstad, G. Saxena, J. Chen, and A. Shalev (2009)
J. Biol. Chem.
284, 16898-16905
|Abstract »|Full Text »|PDF »
Upregulation of the Mammalian Target of Rapamycin Complex 1 Pathway by Ras Homolog Enriched in Brain in Pancreatic {beta}-Cells Leads to Increased {beta}-Cell Mass and Prevention of Hyperglycemia.
S. Hamada, K. Hara, T. Hamada, H. Yasuda, H. Moriyama, R. Nakayama, M. Nagata, and K. Yokono (2009)
Diabetes
58, 1321-1332
|Abstract »|Full Text »|PDF »
TRPM2 Functions as a Lysosomal Ca2+-Release Channel in {beta} Cells.
I. Lange, S. Yamamoto, S. Partida-Sanchez, Y. Mori, A. Fleig, and R. Penner (2009)
Science Signaling
2, ra23
|Abstract »|Full Text »|PDF »
Degradation of cAMP-Responsive Element-Binding Protein by the Ubiquitin-Proteasome Pathway Contributes to Glucotoxicity in {beta}-Cells and Human Pancreatic Islets.
S. Costes, B. Vandewalle, C. Tourrel-Cuzin, C. Broca, N. Linck, G. Bertrand, J. Kerr-Conte, B. Portha, F. Pattou, J. Bockaert, et al. (2009)
Diabetes
58, 1105-1115
|Abstract »|Full Text »|PDF »
Absence of Caspase-3 Protects Pancreatic {beta}-Cells from c-Myc-induced Apoptosis without Leading to Tumor Formation.
A. Radziszewska, S. A. Schroer, D. Choi, P. Tajmir, N. Radulovich, J. C. Ho, L. Wang, N. Liadis, R. Hakem, M.-S. Tsao, et al. (2009)
J. Biol. Chem.
284, 10947-10956
|Abstract »|Full Text »|PDF »
Noncanonical Activation of Akt/Protein Kinase B in {beta}-Cells by the Incretin Hormone Glucose-dependent Insulinotropic Polypeptide.
S. B. Widenmaier, A. V. Sampaio, T. M. Underhill, and C. H. S. McIntosh (2009)
J. Biol. Chem.
284, 10764-10773
|Abstract »|Full Text »|PDF »
Connective Tissue Growth Factor (CTGF) Inactivation Leads to Defects in Islet Cell Lineage Allocation and {beta}-Cell Proliferation during Embryogenesis.
L. A. Crawford, M. A. Guney, Y. A. Oh, R. A. DeYoung, D. M. Valenzuela, A. J. Murphy, G. D. Yancopoulos, K. M. Lyons, D. R. Brigstock, A. Economides, et al. (2009)
Mol. Endocrinol.
23, 324-336
|Abstract »|Full Text »|PDF »
Impact of Small-Molecule Glucokinase Activator on Glucose Metabolism and {beta}-Cell Mass.
A. Nakamura, Y. Terauchi, S. Ohyama, J. Kubota, H. Shimazaki, T. Nambu, I. Takamoto, N. Kubota, J. Eiki, N. Yoshioka, et al. (2009)
Endocrinology
150, 1147-1154
|Abstract »|Full Text »|PDF »
Glycogen Synthase Kinase-3 and Mammalian Target of Rapamycin Pathways Contribute to DNA Synthesis, Cell Cycle Progression, and Proliferation in Human Islets.
H. Liu, M. S. Remedi, K. L. Pappan, G. Kwon, N. Rohatgi, C. A. Marshall, and M. L. McDaniel (2009)
Diabetes
58, 663-672
|Abstract »|Full Text »|PDF »
Gene Silencing of Phogrin Unveils Its Essential Role in Glucose-Responsive Pancreatic {beta}-Cell Growth.
S. Torii, N. Saito, A. Kawano, N. Hou, K. Ueki, R. N. Kulkarni, and T. Takeuchi (2009)
Diabetes
58, 682-692
|Abstract »|Full Text »|PDF »
pVHL is a regulator of glucose metabolism and insulin secretion in pancreatic {beta} cells.
J. Zehetner, C. Danzer, S. Collins, K. Eckhardt, P. A. Gerber, P. Ballschmieter, J. Galvanovskis, K. Shimomura, F. M. Ashcroft, B. Thorens, et al. (2008)
Genes & Dev.
22, 3135-3146
|Abstract »|Full Text »|PDF »
Selective Small-Molecule Agonists of G Protein-Coupled Receptor 40 Promote Glucose-Dependent Insulin Secretion and Reduce Blood Glucose in Mice.
C. P. Tan, Y. Feng, Y.-P. Zhou, G. J. Eiermann, A. Petrov, C. Zhou, S. Lin, G. Salituro, P. Meinke, R. Mosley, et al. (2008)
Diabetes
57, 2211-2219
|Abstract »|Full Text »|PDF »
Increased Pancreatic Beta-Cell Apoptosis following Fetal and Neonatal Exposure to Nicotine Is Mediated via the Mitochondria.
J. E. Bruin, H. C. Gerstein, K. M. Morrison, and A. C. Holloway (2008)
Toxicol. Sci.
103, 362-370
|Abstract »|Full Text »|PDF »
Glucose and leptin induce apoptosis in human {beta}-cells and impair glucose-stimulated insulin secretion through activation of c-Jun N-terminal kinases.
K. Maedler, F. T. Schulthess, C. Bielman, T. Berney, C. Bonny, M. Prentki, M. Y. Donath, and R. Roduit (2008)
FASEB J
22, 1905-1913
|Abstract »|Full Text »|PDF »
{beta}-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic {beta} cells.
N. Sonoda, T. Imamura, T. Yoshizaki, J. L. Babendure, J.-C. Lu, and J. M. Olefsky (2008)
PNAS
105, 6614-6619
|Abstract »|Full Text »|PDF »
Rab GTPase-Activating Protein AS160 Is a Major Downstream Effector of Protein Kinase B/Akt Signaling in Pancreatic {beta}-Cells.
K. Bouzakri, P. Ribaux, A. Tomas, G. Parnaud, K. Rickenbach, and P. A. Halban (2008)
Diabetes
57, 1195-1204
|Abstract »|Full Text »|PDF »
Thioredoxin-Interacting Protein: A Critical Link Between Glucose Toxicity and {beta}-Cell Apoptosis.
J. Chen, G. Saxena, I. N. Mungrue, A. J. Lusis, and A. Shalev (2008)
Diabetes
57, 938-944
|Abstract »|Full Text »|PDF »
mTOR Inhibition by Rapamycin Prevents {beta}-Cell Adaptation to Hyperglycemia and Exacerbates the Metabolic State in Type 2 Diabetes.
M. Fraenkel, M. Ketzinel-Gilad, Y. Ariav, O. Pappo, M. Karaca, J. Castel, M.-F. Berthault, C. Magnan, E. Cerasi, N. Kaiser, et al. (2008)
Diabetes
57, 945-957
|Abstract »|Full Text »|PDF »
Transcription Factor 7-Like 2 Regulates {beta}-Cell Survival and Function in Human Pancreatic Islets.
L. Shu, N. S. Sauter, F. T. Schulthess, A. V. Matveyenko, J. Oberholzer, and K. Maedler (2008)
Diabetes
57, 645-653
|Abstract »|Full Text »|PDF »
Free triiodothyronine plasma concentrations are positively associated with insulin secretion in euthyroid individuals.
E. Ortega, J. Koska, N. Pannacciulli, J. C Bunt, and J. Krakoff (2008)
Eur. J. Endocrinol.
158, 217-221
|Abstract »|Full Text »|PDF »
The Role for Endoplasmic Reticulum Stress in Diabetes Mellitus.
ICA512 signaling enhances pancreatic -cell proliferation by regulating cyclins D through STATs.
H. Mziaut, S. Kersting, K.-P. Knoch, W.-H. Fan, M. Trajkovski, K. Erdmann, H. Bergert, F. Ehehalt, H.-D. Saeger, and M. Solimena (2008)
PNAS
105, 674-679
|Abstract »|Full Text »|PDF »
An Illustrated Review of Early Pancreas Development in the Mouse.
M. C. Jorgensen, J. Ahnfelt-Ronne, J. Hald, O. D. Madsen, P. Serup, and J. Hecksher-Sorensen (2007)
Endocr. Rev.
28, 685-705
|Abstract »|Full Text »|PDF »
PAS kinase is required for normal cellular energy balance.
H.-X. Hao, C. M. Cardon, W. Swiatek, R. C. Cooksey, T. L. Smith, J. Wilde, S. Boudina, E. D. Abel, D. A. McClain, and J. Rutter (2007)
PNAS
104, 15466-15471
|Abstract »|Full Text »|PDF »
Regulated Autophagy Controls Hormone Content in Secretory-Deficient Pancreatic Endocrine {beta}-Cells.
B. J. Marsh, C. Soden, C. Alarcon, B. L. Wicksteed, K. Yaekura, A. J. Costin, G. P. Morgan, and C. J. Rhodes (2007)
Mol. Endocrinol.
21, 2255-2269
|Abstract »|Full Text »|PDF »
Distinct In Vivo Roles of Caspase-8 in {beta}-Cells in Physiological and Diabetes Models.
N. Liadis, L. Salmena, E. Kwan, P. Tajmir, S. A. Schroer, A. Radziszewska, X. Li, L. Sheu, M. Eweida, S. Xu, et al. (2007)
Diabetes
56, 2302-2311
|Abstract »|Full Text »|PDF »
Mechanisms involved in the cytotoxic and cytoprotective actions of saturated versus monounsaturated long-chain fatty acids in pancreatic {beta}-cells.
E. Diakogiannaki, S. Dhayal, C. E Childs, P. C Calder, H. J Welters, and N. G Morgan (2007)
J. Endocrinol.
194, 283-291
|Abstract »|Full Text »|PDF »
The Actions of a Novel Potent Islet {beta}-Cell Specific ATP-Sensitive K+ Channel Opener Can Be Modulated by Syntaxin-1A Acting on Sulfonylurea Receptor 1.
B. Ng, Y. Kang, C. L. Elias, Y. He, H. Xie, J. B. Hansen, P. Wahl, and H. Y. Gaisano (2007)
Diabetes
56, 2124-2134
|Abstract »|Full Text »|PDF »
Fetal and neonatal nicotine exposure and postnatal glucose homeostasis: identifying critical windows of exposure.
J. E Bruin, L. D Kellenberger, H. C Gerstein, K. M Morrison, and A. C Holloway (2007)
J. Endocrinol.
194, 171-178
|Abstract »|Full Text »|PDF »
SORCS1: A Novel Human Type 2 Diabetes Susceptibility Gene Suggested by the Mouse.
M. O. Goodarzi, D. M. Lehman, K. D. Taylor, X. Guo, J. Cui, M. J. Quinones, S. M. Clee, B. S. Yandell, J. Blangero, W. A. Hsueh, et al. (2007)
Diabetes
56, 1922-1929
|Abstract »|Full Text »|PDF »
SOX6 Suppresses Cyclin D1 Promoter Activity by Interacting with beta-Catenin and Histone Deacetylase 1, and Its Down-regulation Induces Pancreatic beta-Cell Proliferation.
H. Iguchi, Y. Urashima, Y. Inagaki, Y. Ikeda, M. Okamura, T. Tanaka, A. Uchida, T. T. Yamamoto, T. Kodama, and J. Sakai (2007)
J. Biol. Chem.
282, 19052-19061
|Abstract »|Full Text »|PDF »
The emerging role of FOXO transcription factors in pancreatic {beta} cells.
Transcriptional Regulation of the Endoplasmic Reticulum Stress Gene Chop in Pancreatic Insulin-Producing Cells.
P. Pirot, F. Ortis, M. Cnop, Y. Ma, L. M. Hendershot, D. L. Eizirik, and A. K. Cardozo (2007)
Diabetes
56, 1069-1077
|Abstract »|Full Text »|PDF »
The Fas pathway is involved in pancreatic beta cell secretory function.
D. M. Schumann, K. Maedler, I. Franklin, D. Konrad, J. Storling, M. Boni-Schnetzler, A. Gjinovci, M. O. Kurrer, B. R. Gauthier, D. Bosco, et al. (2007)
PNAS
104, 2861-2866
|Abstract »|Full Text »|PDF »
Resveratrol Binds to the Sulfonylurea Receptor (SUR) and Induces Apoptosis in a SUR Subtype-specific Manner.
A. Hambrock, C. B. de Oliveira Franz, S. Hiller, A. Grenz, S. Ackermann, D. U. Schulze, G. Drews, and H. Osswald (2007)
J. Biol. Chem.
282, 3347-3356
|Abstract »|Full Text »|PDF »
Molecular regulation of pancreatic {beta}-cell mass development, maintenance, and expansion.
Acylated and Unacylated Ghrelin Promote Proliferation and Inhibit Apoptosis of Pancreatic {beta}-Cells and Human Islets: Involvement of 3',5'-Cyclic Adenosine Monophosphate/Protein Kinase A, Extracellular Signal-Regulated Kinase 1/2, and Phosphatidyl Inositol 3-Kinase/Akt Signaling.
R. Granata, F. Settanni, L. Biancone, L. Trovato, R. Nano, F. Bertuzzi, S. Destefanis, M. Annunziata, M. Martinetti, F. Catapano, et al. (2007)
Endocrinology
148, 512-529
|Abstract »|Full Text »|PDF »
Hepatocyte growth factor protects rat RINm5F cell line against free fatty acid-induced apoptosis by counteracting oxidative stress.
C. Santangelo, P. Matarrese, R. Masella, M. C. Di Carlo, A. Di Lillo, B. Scazzocchio, E. Vecci, W. Malorni, R. Perfetti, and E. Anastasi (2007)
J. Mol. Endocrinol.
38, 147-158
|Abstract »|Full Text »|PDF »
Metabolic syndrome: a fata morgana?.
S. J. L. Bakker, R. T. Gansevoort, and D. de Zeeuw (2007)
Nephrol. Dial. Transplant.
22, 15-20
|Full Text »|PDF »
Pro-Survival Role of Gelsolin in Mouse {beta}-Cells.
Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance.
S. M. Turpin, G. I. Lancaster, I. Darby, M. A. Febbraio, and M. J. Watt (2006)
Am J Physiol Endocrinol Metab
291, E1341-E1350
|Abstract »|Full Text »|PDF »
Low Concentration of Interleukin-1{beta} Induces FLICE-Inhibitory Protein-Mediated {beta}-Cell Proliferation in Human Pancreatic Islets..
K. Maedler, D. M. Schumann, N. Sauter, H. Ellingsgaard, D. Bosco, R. Baertschiger, Y. Iwakura, J. Oberholzer, C. B. Wollheim, B. R. Gauthier, et al. (2006)
Diabetes
55, 2713-2722
|Abstract »|Full Text »|PDF »
Fibroblast Growth Factor-21 Improves Pancreatic {beta}-Cell Function and Survival by Activation of Extracellular Signal-Regulated Kinase 1/2 and Akt Signaling Pathways.
W. Wente, A. M. Efanov, M. Brenner, A. Kharitonenkov, A. Koster, G. E. Sandusky, S. Sewing, I. Treinies, H. Zitzer, and J. Gromada (2006)
Diabetes
55, 2470-2478
|Abstract »|Full Text »|PDF »
Type 1, type 1.5, and type 2 diabetes: NOD the diabetes we thought it was.
M. Y. Donath and J. A. Ehses (2006)
PNAS
103, 12217-12218
|Full Text »|PDF »
Maternal developmental stress reduces reproductive success of female offspring in zebra finches.
Impaired NH2-Terminal Processing of Human Proislet Amyloid Polypeptide by the Prohormone Convertase PC2 Leads to Amyloid Formation and Cell Death..
L. Marzban, C. J. Rhodes, D. F. Steiner, L. Haataja, P. A. Halban, and C. B. Verchere (2006)
Diabetes
55, 2192-2201
|Abstract »|Full Text »|PDF »
ERK1/2 Control Phosphorylation and Protein Level of cAMP-Responsive Element-Binding Protein: A Key Role in Glucose-Mediated Pancreatic {beta}-Cell Survival..
S. Costes, C. Broca, G. Bertrand, A.-D. Lajoix, D. Bataille, J. Bockaert, and S. Dalle (2006)
Diabetes
55, 2220-2230
|Abstract »|Full Text »|PDF »
Chronic Inhibition of Mammalian Target of Rapamycin Signaling Downregulates Insulin Receptor Substrates 1 and 2 and AKT Activation: A Crossroad between Cancer and Diabetes?.
S. Di Paolo, A. Teutonico, D. Leogrande, C. Capobianco, and P. F. Schena (2006)
J. Am. Soc. Nephrol.
17, 2236-2244
|Abstract »|Full Text »|PDF »
Pancreatic beta cells lack a low glucose and O2-inducible mitochondrial protein that augments cell survival.
J. Wang, Y. Cao, Y. Chen, Y. Chen, P. Gardner, and D. F. Steiner (2006)
PNAS
103, 10636-10641
|Abstract »|Full Text »|PDF »
Specific Regulation of IRS-2 Expression by Glucose in Rat Primary Pancreatic Islet beta-Cells.
M. K. Lingohr, I. Briaud, L. M. Dickson, J. F. McCuaig, C. Alarcon, B. L. Wicksteed, and C. J. Rhodes (2006)
J. Biol. Chem.
281, 15884-15892
|Abstract »|Full Text »|PDF »
WFS1-deficiency increases endoplasmic reticulum stress, impairs cell cycle progression and triggers the apoptotic pathway specifically in pancreatic {beta}-cells.
T. Yamada, H. Ishihara, A. Tamura, R. Takahashi, S. Yamaguchi, D. Takei, A. Tokita, C. Satake, F. Tashiro, H. Katagiri, et al. (2006)
Hum. Mol. Genet.
15, 1600-1609
|Abstract »|Full Text »|PDF »
Dexamethasone induces cell death in insulin-secreting cells, an effect reversed by exendin-4..
F. Ranta, D. Avram, S. Berchtold, M. Dufer, G. Drews, F. Lang, and S. Ullrich (2006)
Diabetes
55, 1380-1390
|Abstract »|Full Text »|PDF »
Glucose-stimulated DNA Synthesis through Mammalian Target of Rapamycin (mTOR) Is Regulated by KATP Channels: EFFECTS ON CELL CYCLE PROGRESSION IN RODENT ISLETS.
G. Kwon, C. A. Marshall, H. Liu, K. L. Pappan, M. S. Remedi, and M. L. McDaniel (2006)
J. Biol. Chem.
281, 3261-3267
|Abstract »|Full Text »|PDF »
The Forkhead Transcription Factor Foxo1 Bridges the JNK Pathway and the Transcription Factor PDX-1 through Its Intracellular Translocation.
D. Kawamori, H. Kaneto, Y. Nakatani, T.-a. Matsuoka, M. Matsuhisa, M. Hori, and Y. Yamasaki (2006)
J. Biol. Chem.
281, 1091-1098
|Abstract »|Full Text »|PDF »
A Functional Variant in the Human Betacellulin Gene Promoter Is Associated With Type 2 Diabetes.
Y. Nakano, H. Furuta, A. Doi, S. Matsuno, T. Nakagawa, H. Shimomura, S. Sakagashira, Y. Horikawa, M. Nishi, H. Sasaki, et al. (2005)
Diabetes
54, 3560-3566
|Abstract »|Full Text »|PDF »
