Inadequate compensatory β cell hyperplasia in insulin-resistant states triggers the development of overt diabetes. The mechanisms that underlie this crucial adaptive response are not fully defined. Here we show that the compensatory islet-growth response to insulin resistance in 2 models — insulin receptor (IR)/IR substrate–1 (IRS-1) double heterozygous mice and liver-specific IR KO (LIRKO) mice — is severely restricted by PDX-1 heterozygosity. Six-month-old IR/IRS-1 and LIRKO mice both showed up to a 10-fold increase in β cell mass, which involved epithelial-to-mesenchymal transition. In both models, superimposition of PDX-1 haploinsufficiency upon the background of insulin resistance completely abrogated the adaptive islet hyperplastic response, and instead the β cells showed apoptosis resulting in premature death of the mice. This study shows that, in postdevelopmental states of β cell growth, PDX-1 is a critical regulator of β cell replication and is required for the compensatory response to insulin resistance.
Rohit N. Kulkarni, Ulupi S. Jhala, Jonathon N. Winnay, Stan Krajewski, Marc Montminy, C. Ronald Kahn
Title and authors | Publication | Year |
---|---|---|
Revealing the biological features of the axolotl pancreas as a new research model
Ma H, Peng G, Hu Y, Lu B, Zheng Y, Wu Y, Feng W, Shi Y, Pan X, Song L, Stützer I, Liu Y, Fei J |
Frontiers in Cell and Developmental Biology | 2025 |
Rare, Tightly-Bound, Multi-Cellular Clusters in the Pancreatic Ducts of Adult Mice Function Like Progenitor Cells and Survive and Proliferate After Acinar Cell Injury
Tremblay JR, Ortiz JA, Quijano JC, Zook HN, Erdem N, LeBon JM, Li W, Jou K, Tsark W, Mann JR, Kozlowski MT, Tirrell DA, Esni F, Engle DD, Riggs AD, Ku HT |
STEM CELLS | 2024 |
TRPM7 kinase is required for insulin production and compensatory islet responses during obesity
Noushafarin Khajavi, Andreas Beck, Klea Ricku, Philipp Beyerle, Katharina Jacob, Sabrina Syamsul, Anouar Belkacemi, Houssein Salah, Tanja Popp, Aaron Novikoff, Andreas Breit, Vladimir Chubanov, Timo Müller, Susanna Zierler, Thomas Gudermann |
JCI Insight | 2023 |
β−Arrestins: Structure, Function, Physiology, and Pharmacological Perspectives
Wess J, Oteng AB, Rivera-Gonzalez O, Gurevich EV, Gurevich VV |
Pharmacological reviews | 2023 |
FoxO1 as a tissue-specific therapeutic target for type 2 diabetes
Teaney NA, Cyr NE |
Frontiers in Endocrinology | 2023 |
Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus
H Kaneto, T Kimura, M Shimoda, A Obata, J Sanada, Y Fushimi, T Matsuoka, K Kaku |
Biomedicines | 2022 |
PDX-1: A Promising Therapeutic Target to Reverse Diabetes.
Zhang Y, Fang X, Wei J, Miao R, Wu H, Ma K, Tian J |
Biomolecules | 2022 |
Resistance exercise training improves glucose homeostasis by enhancing insulin secretion in C57BL/6 mice
GA Bronczek, GM Soares, JF de Barros, JF Vettorazzi, MA Kurauti, E Marconato-Júnior, L Zangerolamo, C Marmentini, AC Boschero, JM Costa-Júnior |
Scientific Reports | 2021 |
Adipose Tissue Macrophages Modulate Obesity-Associated β Cell Adaptations through Secreted miRNA-Containing Extracellular Vesicles
H Gao, Z Luo, Z Jin, Y Ji, W Ying |
Cells | 2021 |
Excessive Intake of High-Fructose Corn Syrup Drinks Induces Impaired Glucose Tolerance
H Hattori, Y Hanai, Y Oshima, H Kataoka, N Eto |
Biomedicines | 2021 |
β-Arrestin-1 is required for adaptive β-cell mass expansion during obesity
LF Barella, M Rossi, SP Pydi, J Meister, S Jain, Y Cui, O Gavrilova, G Fulgenzi, L Tessarollo, J Wess |
Nature Communications | 2021 |
Menin‐regulated Pbk controls high fat diet‐induced compensatory beta cell proliferation
J Ma, B Xing, Y Cao, X He, KE Bennett, C Tong, C An, T Hojnacki, Z Feng, S Deng, S Ling, G Xie, Y Wu, Y Ren, M Yu, BW Katona, H Li, A Naji, X Hua |
EMBO Molecular Medicine | 2021 |
Pancreatic and duodenal homeobox-1 (PDX1) contributes to β-cell mass expansion and proliferation induced by Akt/PKB pathway
MA Jara, JP Werneck-De-Castro, C Lubaczeuski, JD Johnson, E Bernal-Mizrachi |
Islets | 2020 |
MicroRNA-17-92 Regulates Beta-Cell Restoration After Streptozotocin Treatment
S Wan, J Zhang, X Chen, J Lang, L Li, F Chen, L Tian, Y Meng, X Yu |
Frontiers in Endocrinology | 2020 |
Elevated β-cell stress levels promote severe diabetes development in mice with MODY4
BM Trojanowski, HH Salem, H Neubauer, E Simon, M Wagner, R Dorajoo, BO Boehm, L Labriola, T Wirth, B Baumann |
Journal of Endocrinology | 2020 |
Danzhi Jiangtang Capsule Mediates NIT-1 Insulinoma Cell Proliferation and Apoptosis by GLP-1/Akt Signaling Pathway
YJ Wu, YB Wu, ZH Fang, MQ Chen, YF Wang, CY Wu, MA Lv |
Evidence-Based Complementary and Alternative Medicine | 2019 |
The epigenetics of diabetes, obesity, overweight and cardiovascular disease
HO Smail |
AIMS Genetics | 2019 |
How, When, and Where Do Human β-Cells Regenerate?
G Basile, RN Kulkarni, NG Morgan |
Current Diabetes Reports | 2019 |
m6A mRNA methylation regulates human β-cell biology in physiological states and in type 2 diabetes
DF Jesus, Z Zhang, S Kahraman, NK Brown, M Chen, J Hu, MK Gupta, C He, RN Kulkarni |
2019 | |
Intracellular lipid metabolism impairs β-cell compensation during diet-induced obesity
Risheng Ye, Ruth Gordillo, Mengle Shao, Toshiharu Onodera, Zhe Chen, Shiuhwei Chen, Xiaoli Lin, Jeffrey A. SoRelle, Xiaohong Li, Miao Tang, mark keller, Regina Kuliawat, Alan D. Attie, Rana Gupta, William L. Holland, Bruce Beutler, Joachim Herz, Philipp E. Scherer |
Journal of Clinical Investigation | 2018 |
A PDX1-ATF transcriptional complex governs β cell survival during stress
CA Juliana, J Yang, CE Cannon, AL Good, MW Haemmerle, DA Stoffers |
Molecular Metabolism | 2018 |
Increases in bioactive lipids accompany early metabolic changes associated with β-cell expansion in response to short-term high-fat diet
MD Seferovic, CA Beamish, RE Mosser, SE Townsend, K Pappan, V Poitout, KM Aagaard, M Gannon |
American journal of physiology. Endocrinology and metabolism | 2018 |
A Comprehensive Survey of the Roles of Highly Disordered Proteins in Type 2 Diabetes
Z Du, V Uversky |
International journal of molecular sciences | 2017 |
Defining a Novel Role for the Pdx1 Transcription Factor in Islet β-Cell Maturation and Proliferation During Weaning
JM Spaeth, M Gupte, M Perelis, YP Yang, H Cyphert, S Guo, JH Liu, M Guo, J Bass, MA Magnuson, C Wright, R Stein |
Diabetes | 2017 |
Adipocyte Dynamics and Reversible Metabolic Syndrome in Mice with an Inducible Adipocyte-Specific Deletion of the Insulin Receptor
M Sakaguchi, S Fujisaka, W Cai, JN Winnay, M Konishi, BT O'Neill, M Li, R García-Martín, H Takahashi, J Hu, RN Kulkarni, CR Kahn |
Cell Metabolism | 2017 |
Impaired Insulin Signaling is Associated with Hepatic Mitochondrial Dysfunction in IR+/−-IRS-1+/− Double Heterozygous (IR-IRS1dh) Mice
A Franko, A Kunze, M Böse, JC Kleist-Retzow, M Paulsson, U Hartmann, R Wiesner |
International journal of molecular sciences | 2017 |
Tcf7l2 plays pleiotropic roles in the control of glucose homeostasis, pancreas morphology, vascularization and regeneration
Nicola Facchinello, Estefania Tarifeño-Saldivia, Enrico Grisan, Marco Schiavone, Margherita Peron, Alessandro Mongera, Olivier Ek, Nicole Schmitner, Dirk Meyer, Bernard Peers, Natascia Tiso, Francesco Argenton |
Scientific Reports | 2017 |
The prolyl isomerase Pin1 increases β-cell proliferation and enhances insulin secretion
Y Nakatsu, K Mori, Y Matsunaga, T Yamamotoya, K Ueda, Y Inoue, K Mitsuzaki-Miyoshi, H Sakoda, M Fujishiro, S Yamaguchi, A Kushiyama, H Ono, H Ishihara, T Asano |
The Journal of biological chemistry | 2017 |
Genetic Disruption of Adenosine Kinase in Mouse Pancreatic β-Cells Protects Against High-Fat Diet–Induced Glucose Intolerance
G Navarro, Y Abdolazimi, Z Zhao, H Xu, S Lee, NA Armstrong, JP Annes |
Diabetes | 2017 |
Cooperative function of Pdx1 and Oc1 in multipotent pancreatic progenitors impacts postnatal islet maturation and adaptability
PA Kropp, JC Dunn, BA Carboneau, DA Stoffers, M Gannon |
American journal of physiology. Endocrinology and metabolism | 2017 |
Trimeprazine increases IRS2 in human islets and promotes pancreatic beta-cell growth and function in mice
Alexandra Kuznetsova, Yue Yu, Jennifer Hollister-Lock, Lynn Opare-Addo, Aldo Rozzo, Marianna Sadagurski, Lisa Norquay, Jessica E. Reed, Ilham El Khattabi, Susan Bonner-Weir, Gordon C. Weir, Arun Sharma, Morris F. White |
JCI Insight | 2016 |
Inhibition of TGF-β Signaling Promotes Human Pancreatic β-Cell Replication
S Dhawan, E Dirice, RN Kulkarni, A Bhushan |
Diabetes | 2016 |
Exendin-4 enhances expression of Neurod1 and Glut2 in insulin-producing cells derived from mouse embryonic stem cells
Q Zhao, Y Yang, J Hu, Z Shan, Y Wu, L Lei |
Archives of Medical Science : AMS | 2016 |
Threshold-Dependent Cooperativity of Pdx1 and Oc1 in Pancreatic Progenitors Establishes Competency for Endocrine Differentiation and β-Cell Function
KD Henley, DE Stanescu, PA Kropp, CV Wright, KJ Won, DA Stoffers, M Gannon |
Cell Reports | 2016 |
Pancreatic Islet Responses to Metabolic Trauma:
SJ Burke, MD Karlstad, JJ Collier |
Shock | 2016 |
Adipose- and muscle-derived Wnts trigger pancreatic β-cell adaptation to systemic insulin resistance
K Kozinski, M Jazurek, P Dobrzyn, J Janikiewicz, K Kolczynska, A Gajda, A Dobrzyn |
Scientific Reports | 2016 |
Proinflammatory Cytokines Induce Endocrine Differentiation in Pancreatic Ductal Cells via STAT3-Dependent NGN3 Activation
IA Valdez, E Dirice, MK Gupta, J Shirakawa, AK Teo, RN Kulkarni |
Cell Reports | 2016 |
Expression of pancreatic and duodenal homeobox1 (PDX1) protein in the interior and exterior regions of the intestine, revealed by development and analysis of Pdx1 knockout mice
H Hashimoto, T Kamisako, T Kagawa, S Haraguchi, M Yagoto, R Takahashi, K Kawai, H Suemizu |
Laboratory animal research | 2015 |
Role of Pancreatic Transcription Factors in Maintenance of Mature β-Cell Function
H Kaneto, T Matsuoka |
International journal of molecular sciences | 2015 |
WS6 induces both alpha and beta cell proliferation without affecting differentiation or viability
BP Boerner, NM George, SU Mir, NE Sarvetnick |
Endocrine Journal | 2015 |
Differences in insulin biosynthesis pathway between small and large islets do not correspond to insulin secretion
HH Huang, L Stehno-Bittel |
Islets | 2015 |
Vitamin A Deficiency Causes Hyperglycemia and Loss of Pancreatic β-Cell Mass
SE Trasino, YD Benoit, LJ Gudas |
The Journal of biological chemistry | 2014 |
Mangiferin Facilitates Islet Regeneration and β-Cell Proliferation through Upregulation of Cell Cycle and β-Cell Regeneration Regulators
HL Wang, CY Li, B Zhang, YD Liu, BM Lu, Z Shi, N An, LK Zhao, JJ Zhang, JK Bao, Y Wang |
International journal of molecular sciences | 2014 |
Sox17 Regulates Insulin Secretion in the Normal and Pathologic Mouse β Cell
D Jonatan, JR Spence, AM Method, M Kofron, K Sinagoga, L Haataja, P Arvan, GH Deutsch, JM Wells, Y Ikeda |
PloS one | 2014 |
Pancreatic and Duodenal Homeobox Protein 1 (Pdx-1) Maintains Endoplasmic Reticulum Calcium Levels through Transcriptional Regulation of Sarco-endoplasmic Reticulum Calcium ATPase 2b (SERCA2b) in the Islet Cell
JS Johnson, T Kono, X Tong, WR Yamamoto, A Zarain-Herzberg, MJ Merrins, LS Satin, P Gilon, C Evans-Molina |
The Journal of biological chemistry | 2014 |
A dual role of lipasin (betatrophin) in lipid metabolism and glucose homeostasis: consensus and controversy
R Zhang, AB Abou-Samra |
Cardiovascular Diabetology | 2014 |
MicroRNA-200 Is Induced by Thioredoxin-interacting Protein and Regulates Zeb1 Protein Signaling and Beta Cell Apoptosis
SR Filios, G Xu, J Chen, K Hong, G Jing, A Shalev |
The Journal of biological chemistry | 2014 |
Protective effect of Schisandrae chinensis oil on pancreatic β-cells in diabetic rats.
An L, Wang Y, Wang C, Fan M, Han X, Xu G, Yuan G, Li H, Sheng Y, Wang M, Sun J, Zhan J, Sun H, Li N, Ding F, Du P |
Endocrine | 2014 |
Peroxisome proliferator-activated receptor γ (PPARγ) and its target genes are downstream effectors of FoxO1 protein in islet β-cells: mechanism of β-cell compensation and failure
D Gupta, AA Leahy, N Monga, M Peshavaria, TL Jetton, JL Leahy |
The Journal of biological chemistry | 2013 |
Beta cell dysfunction and insulin resistance
ME Cerf |
Frontiers in Endocrinology | 2013 |
The role of FOXO1 in β-cell failure and type 2 diabetes mellitus
T Kitamura |
Nature Reviews Endocrinology | 2013 |
The transcriptional co-regulator HCF-1 is required for INS-1 β-cell glucose-stimulated insulin secretion
TN Iwata, TJ Cowley, M Sloma, Y Ji, H Kim, L Qi, SS Lee |
PloS one | 2013 |
Betatrophin: A Hormone that Controls Pancreatic β Cell Proliferation
P Yi, JS Park, DA Melton |
Cell | 2013 |
Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes
V Nesca, C Guay, C Jacovetti, V Menoud, ML Peyot, DR Laybutt, M Prentki, R Regazzi |
Diabetologia | 2013 |
Neonatal exendin-4 reduces growth, fat deposition and glucose tolerance during treatment in the intrauterine growth-restricted lamb
KL Gatford, SA Sulaiman, SN Mohammad, MJ de Blasio, ML Harland, RA Simmons, JA Owens |
PloS one | 2013 |
Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development
SM Green-Mitchell, SA Tersey, BK Cole, K Ma, NS Kuhn, TD Cunningham, NA Maybee, SK Chakrabarti, M McDuffie, DA Taylor-Fishwick, RG Mirmira, JL Nadler, MA Morris |
PloS one | 2013 |
PDX1 in Ducts Is Not Required for Postnatal Formation of -Cells but Is Necessary for Their Subsequent Maturation
L Guo, A Inada, C Aguayo-Mazzucato, J Hollister-Lock, Y Fujitani, GC Weir, CV Wright, A Sharma, S Bonner-Weir |
Diabetes | 2013 |
Imaging Beta Cell Regeneration and Interactions with Islet Vasculature in Transparent Adult Zebrafish
LG Moss, TV Caplan, JB Moss |
Zebrafish | 2013 |
β-Cell Regeneration Mediated by Human Bone Marrow Mesenchymal Stem Cells
A Milanesi, JW Lee, Z Li, SD Sacco, V Villani, V Cervantes, L Perin, JS Yu |
PloS one | 2012 |
Fetal PGC-1α overexpression programs adult pancreatic β-cell dysfunction
B Valtat, JP Riveline, P Zhang, A Singh-Estivalet, M Armanet, N Venteclef, A Besseiche, DP Kelly, F Tronche, P Ferré, JF Gautier, B Bréant, B Blondeau |
Diabetes | 2012 |
A Simple Matter of Life and Death—The Trials of Postnatal Beta-Cell Mass Regulation
E Tarabra, S Pelengaris, M Khan |
International Journal of Endocrinology | 2012 |
Adenosine kinase inhibition selectively promotes rodent and porcine islet β-cell replication
JP Annes, JH Ryu, K Lam, PJ Carolan, K Utz, J Hollister-Lock, AC Arvanites, LL Rubin, G Weir, DA Melton |
Proceedings of the National Academy of Sciences | 2012 |
Pdx1 Is Post-Translationally Modified In vivo and Serine 61 Is the Principal Site of Phosphorylation
T Frogne, KB Sylvestersen, S Kubicek, ML Nielsen, J Hecksher-Sørensen, M Federici |
PloS one | 2012 |
Differential regulation of embryonic and adult β cell replication
U Gunasekaran, CW Hudgens, BT Wright, MF Maulis, M Gannon |
Cell cycle (Georgetown, Tex.) | 2012 |
Development of novel cell lines of diabetic dysfunction model fit for cell-based screening tests of medicinal materials
M Saito, A Hayakawa, N Inagaki, H Matsuoka |
Cytotechnology | 2012 |
Decreased expression of insulin and increased expression of pancreatic transcription factor PDX-1 in islets in patients with liver cirrhosis: a comparative investigation using human autopsy specimens
M Sakata, A Kawahara, T Kawaguchi, J Akiba, T Taira, E Taniguchi, M Abe, H Koga, M Kage, M Sata |
Journal of Gastroenterology | 2012 |
PDX1-engineered embryonic stem cell-derived insulin producing cells regulate hyperglycemia in diabetic mice
SP Raikwar, N Zavazava |
Transplantation Research | 2012 |
Hepatocyte-specific Ptpn6 deletion protects from obesity-linked hepatic insulin resistance
E Xu, A Charbonneau, Y Rolland, K Bellmann, L Pao, KA Siminovitch, BG Neel, N Beauchemin, A Marette |
Diabetes | 2012 |
40 Isoform of p53 Controls -Cell Proliferation and Glucose Homeostasis in Mice
C Hinault, D Kawamori, CW Liew, B Maier, J Hu, SR Keller, RG Mirmira, H Scrable, RN Kulkarni |
Diabetes | 2011 |
Endoplasmic Reticulum Oxidoreductin-1-Like β (ERO1lβ) Regulates Susceptibility to Endoplasmic Reticulum Stress and Is Induced by Insulin Flux in β-Cells
C Khoo, J Yang, G Rajpal, Y Wang, J Liu, P Arvan, DA Stoffers |
Endocrinology | 2011 |
Altered Insulin Receptor Signalling and β-Cell Cycle Dynamics in Type 2 Diabetes Mellitus
F Folli, T Okada, C Perego, J Gunton, CW Liew, M Akiyama, A D'Amico, SL Rosa, C Placidi, R Lupi, P Marchetti, G Sesti, M Hellerstein, L Perego, RN Kulkarni |
PloS one | 2011 |
Control of Pancreatic β Cell Regeneration by Glucose Metabolism
S Porat, N Weinberg-Corem, S Tornovsky-Babaey, R Schyr-Ben-Haroush, A Hija, M Stolovich-Rain, D Dadon, Z Granot, V Ben-Hur, P White, CA Girard, R Karni, KH Kaestner, FM Ashcroft, MA Magnuson, A Saada, J Grimsby, B Glaser, Y Dor |
Cell Metabolism | 2011 |
Effects of diabetes mellitus on the rat liver during the postmenopausal period
D Unal, S Aksak, Z Halici, O Sengul, B Polat, B Unal, M Halici |
Journal Of Molecular Histology | 2011 |
Early-Life Origins of Type 2 Diabetes: Fetal Programming of the Beta-Cell Mass
B Portha, A Chavey, J Movassat |
Experimental Diabetes Research | 2011 |
Exendin-4 increases histone acetylase activity and reverses epigenetic modifications that silence Pdx1 in the intrauterine growth retarded rat
SE Pinney, LJ Santos, Y Han, DA Stoffers, RA Simmons |
Diabetologia | 2011 |
The Unique Hypusine Modification of eIF5A Promotes Islet beta Cell Inflammation and Dysfunction
Bernhard Maier, Takeshi Ogihara, Anthony Trace, Sarah A. Tersey, Reiesha D. Robbins, Swarup K. Chakrabarti, Craig S. Nunemaker, Natalie D. Stull, Catherine A. Taylor, John E. Thompson, Richard S. Dondero, Eli C. Lewis, Charles A. Dinarello, Jerry L. Nadler, Raghavendra G. Mirmira |
Journal of Clinical Investigation | 2010 |
Pdx1 regulation of pancreatic beta cell survival and function is modulated by the ubiquitin ligase adaptor Pcif1
Kathryn Claiborn, Mira Sachdeva, Corey Cannon, David Groff, Jeffrey Singer, Doris Stoffers |
Journal of Clinical Investigation | 2010 |
Interrupting Nix upregulation in Pdx1 deficiency prevents apoptotic and necrotic beta-cell death, and murine diabetes
Kei Fujimoro, Eric Ford, Hung Tran, Burton Wice, Seth Crosby, Gerald Dorn, Kenneth Polonsky |
Journal of Clinical Investigation | 2010 |
Erythropoietin protects against diabetes through direct effects on pancreatic beta cells
D Choi, SA Schroer, SY Lu, L Wang, X Wu, Y Liu, Y Zhang, HY Gaisano, KU Wagner, H Wu, R Retnakaran, M Woo |
Journal of Experimental Medicine | 2010 |
Glucose and aging control the quiescence period that follows pancreatic beta cell replication
SJ Salpeter, AM Klein, D Huangfu, J Grimsby, Y Dor |
Development (Cambridge, England) | 2010 |
Mechanisms of non-apoptotic programmed cell death in diabetes and heart failure
GW Dorn |
Cell cycle (Georgetown, Tex.) | 2010 |
Cyclin D2 is essential for the compensatory beta-cell hyperplastic response to insulin resistance in rodents
S Georgia, C Hinault, D Kawamori, J Hu, J Meyer, M Kanji, A Bhushan, RN Kulkarni |
Diabetes | 2010 |
Targeting cyclophilin D and the mitochondrial permeability transition enhances beta-cell survival and prevents diabetes in Pdx1 deficiency
K Fujimoto, Y Chen, KS Polonsky, GW 2nd |
Proceedings of the National Academy of Sciences | 2010 |
Attacking the source: anti-PDX-1 responses in type 1 diabetes
Y Luzardo, CE Mathews |
Laboratory Investigation | 2010 |
Obesity and hyperinsulinemia in a family with pancreatic agenesis and MODY caused by the IPF1 mutation Pro63fsX60
SS Fajans, GI Bell, VP Paz, JE Below, NJ Cox, C Martin, IH Thomas, M Chen |
Translational research : the journal of laboratory and clinical medicine | 2010 |
Glucolipotoxicity age-dependently impairs beta cell function in rats despite a marked increase in beta cell mass
G Fontés, B Zarrouki, DK Hagman, MG Latour, M Semache, V Roskens, PC Moore, M Prentki, CJ Rhodes, TL Jetton, V Poitout |
Diabetologia | 2010 |
Differential Effects of Prenatal and Postnatal Nutritional Environment on β-Cell Mass Development and Turnover in Male and Female Rats
AV Matveyenko, I Singh, BC Shin, S Georgia, SU Devaskar |
Endocrinology | 2010 |
Vagal control of pancreatic β-cell proliferation
J Lausier, WC Diaz, V Roskens, K LaRock, K Herzer, CG Fong, MG Latour, M Peshavaria, TL Jetton |
American journal of physiology. Endocrinology and metabolism | 2010 |
The Effect of Tribbles-Related Protein 3 on ER Stress-Suppressed Insulin Gene Expression in INS-1 Cells
YY Jang, NK Kim, MK Kim, HY Lee, SJ Kim, HS Kim, HY Seo, IK Lee, KG Park |
Korean Diabetes Journal | 2010 |
Minireview: Meeting the demand for insulin: molecular mechanisms of adaptive postnatal beta-cell mass expansion
MM Sachdeva, DA Stoffers |
Molecular Endocrinology | 2009 |
Slow and steady is the key to β-cell replication
K Brennand, D Melton |
Journal of Cellular and Molecular Medicine | 2009 |
Growth factor control of pancreatic islet regeneration and function
A Assmann, C Hinault, RN Kulkarni |
Pediatric Diabetes | 2009 |
Glucose regulates steady-state levels of PDX1 via the reciprocal actions of GSK3 and AKT kinases
RK Humphrey, SM Yu, LE Flores, US Jhala |
The Journal of biological chemistry | 2009 |
Pdx1 and other factors that regulate pancreatic β-cell survival
K Fujimoto, KS Polonsky |
Diabetes, Obesity and Metabolism | 2009 |
Pdx1 (MODY4) regulates pancreatic beta cell susceptibility to ER stress
MM Sachdeva, KC Claiborn, C Khoo, J Yang, DN Groff, RG Mirmira, DA Stoffers |
Proceedings of the National Academy of Sciences | 2009 |
Bmi-1 regulates the Ink4a/Arf locus to control pancreatic β-cell proliferation
S Dhawan, SI Tschen, A Bhushan |
Genes & development | 2009 |
Developmental Origins of Type 2 Diabetes: Progressive Epigenetic Modifications Silence Pdx1
Jun H. Park, Doris A. Stoffers, Robert D. Nicholls, Rebecca A. Simmons |
Journal of Clinical Investigation | 2008 |
Insulin Stimulates Primary β-Cell Proliferation via Raf-1 Kinase
JL Beith, EU Alejandro, JD Johnson |
Endocrinology | 2008 |
Pleiotropic Roles of PDX-1 in the Pancreas
H Kaneto, T Miyatsuka, D Kawamori, TA Matsuoka |
The review of diabetic studies : RDS | 2008 |
In vivo and in vitro studies of a functional peroxisome proliferator-activated receptor gamma response element in the mouse pdx-1 promoter
D Gupta, TL Jetton, RM Mortensen, SZ Duan, M Peshavaria, JL Leahy |
The Journal of biological chemistry | 2008 |
On the origin of the beta cell
JM Oliver-Krasinski, DA Stoffers |
Genes & development | 2008 |
Skp2-mediated p27 degradation plays an essential role in the growth and adaptive expansion of pancreatic beta cells
Lingwen Zhong, Senta Georgia, Shuen-ing Tschen, Keiko Nakayama, Keiichi Nakayama and Anil Bhushan |
Journal of Clinical Investigation | 2007 |
Recovery from diabetes by beta cell regeneration
Tomer Nir, Douglas A. Melton, Yuval Dor |
Journal of Clinical Investigation | 2007 |
From the Cover: Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance
T Okada, CW Liew, J Hu, C Hinault, MD Michael, J Krtzfeldt, C Yin, M Holzenberger, M Stoffel, RN Kulkarni |
Proceedings of the National Academy of Sciences | 2007 |
A feat of metabolic proportions: Pdx1 orchestrates islet development and function in the maintenance of glucose homeostasis
DA Babu, TG Deering, RG Mirmira |
Molecular Genetics and Metabolism | 2007 |
All beta cells contribute equally to islet growth and maintenance
K Brennand, D Huangfu, D Melton |
PLoS Biology | 2007 |
Formation and regeneration of the endocrine pancreas
S Dhawan, S Georgia, A Bhushan |
Current Opinion in Cell Biology | 2007 |
Pancreatic deletion of insulin receptor substrate 2 reduces beta and alpha cell mass and impairs glucose homeostasis in mice
J Cantley, AI Choudhury, H Asare-Anane, C Selman, S Lingard, H Heffron, P Herrera, SJ Persaud, DJ Withers |
Diabetologia | 2007 |
Reversal of Streptozotocin-Induced Diabetes in Mice by Cellular Transduction With Recombinant Pancreatic Transcription Factor Pancreatic Duodenal Homeobox-1: A Novel Protein Transduction Domain-Based Therapy
V Koya, S Lu, YP Sun, DL Purich, MA Atkinson, SW Li, LJ Yang |
Diabetes | 2007 |
Expansion of adult beta-cell mass in response to increased metabolic demand is dependent on HNF-4alpha
RK Gupta, N Gao, RK Gorski, P White, OT Hardy, K Rafiq, JE Brestelli, G Chen, CJ Stoeckert, KH Kaestner |
Genes & development | 2007 |
Extracts of Rehmanniae radix, Ginseng radix and Scutellariae radix improve glucose-stimulated insulin secretion and beta-cell proliferation through IRS2 induction
SM Park, SM Hong, SR Sung, JE Lee, DY Kwon |
Genes & Nutrition | 2007 |
Long-term consumption of fermented soybean-derived Chungkookjang enhances insulinotropic action unlike soybeans in 90% pancreatectomized diabetic rats
DY Kwon, JS Jang, SM Hong, JE Lee, SR Sung, HR Park, S Park |
European Journal of Nutrition | 2007 |
Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity: Oxidative stress in diabetes
P Newsholme, EP Haber, SM Hirabara, EL Rebelato, J Procopio, D Morgan, HC Oliveira-Emilio, AR Carpinelli, R Curi |
The Journal of Physiology | 2007 |
Essential role of Pten in body size determination and pancreatic beta-cell homeostasis in vivo
KT Nguyen, P Tajmir, CH Lin, N Liadis, XD Zhu, M Eweida, G Tolasa-Karaman, F Cai, R Wang, T Kitamura, DD Belsham, MB Wheeler, A Suzuki, TW Mak, M Woo |
Molecular and cellular biology | 2006 |
Insulin protects islets from apoptosis via Pdx1 and specific changes in the human islet proteome
JD Johnson, E Bernal-Mizrachi, EU Alejandro, Z Han, TB Kalynyak, H Li, JL Beith, J Gross, GL Warnock, RR Townsend, MA Permutt, KS Polonsky |
Proceedings of the National Academy of Sciences | 2006 |
Increased Pancreatic β-Cell Proliferation Mediated by CREB Binding Protein Gene Activation
MA Hussain, DL Porras, MH Rowe, JR West, WJ Song, WE Schreiber, FE Wondisford |
Molecular and cellular biology | 2006 |
Diabetes outfoxed by GLP-1?
GG Holz, OG Chepurny |
Science's STKE : signal transduction knowledge environment | 2005 |
Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes
H Kaneto, T Matsuoka, Y Nakatani, D Kawamori, T Miyatsuka, M Matsuhisa, Y Yamasaki |
Journal of Molecular Medicine | 2005 |
Involvement of oxidative stress and the JNK pathway in glucose toxicity
H Kaneto, Y Nakatani, D Kawamori, T Miyatsuka, T Matsuoka |
The review of diabetic studies : RDS | 2005 |
Molecular engineering human hepatocytes into pancreatic beta cells for diabetes therapy
I Cozar-Castellano, AF Stewart |
Proceedings of the National Academy of Sciences | 2005 |