During embryonic development, insulin-like growth factor-II (IGF-II) participates in the regulation of islet growth and differentiation. We generated transgenic mice (C57BL6/SJL) expressing IGF-II in β cells under control of the rat Insulin I promoter in order to study the role of islet hyperplasia and hyperinsulinemia in the development of type 2 diabetes. In contrast to islets from control mice, islets from transgenic mice displayed high levels of IGF-II mRNA and protein. Pancreases from transgenic mice showed an increase in β-cell mass (about 3-fold) and in insulin mRNA levels. However, the organization of cells within transgenic islets was disrupted, with glucagon-producing cells randomly distributed throughout the core. We also observed enhanced glucose-stimulated insulin secretion and glucose utilization in islets from transgenic mice. These mice displayed hyperinsulinemia, mild hyperglycemia, and altered glucose and insulin tolerance tests, and about 30% of these animals developed overt diabetes when fed a high-fat diet. Furthermore, transgenic mice obtained from the N1 backcross to C57KsJ mice showed high islet hyperplasia and insulin resistance, but they also developed fatty liver and obesity. These results indicate that local overexpression of IGF-II in islets might lead to type 2 diabetes and that islet hyperplasia and hypersecretion of insulin might occur early in the pathogenesis of this disease.
Jean-Christophe Devedjian, Monica George, Alba Casellas, Anna Pujol, Joana Visa, Mireia Pelegrín, Laurent Gros, Fatima Bosch
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Short-Term Treatment with Bisphenol-A Leads to Metabolic Abnormalities in Adult Male Mice
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Epigenetic Epidemiology
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2011 | |
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Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society | 2010 |
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Mechanisms of Oncogenesis
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Severe Intrauterine Growth Retardation and Atypical Diabetes Associated with a Translocation Breakpoint Disrupting Regulation of the Insulin-Like Growth Factor 2 Gene
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The Journal of clinical endocrinology and metabolism | 2008 |
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Selective Deletion of Pten in Pancreatic β Cells Leads to Increased Islet Mass and Resistance to STZ-Induced Diabetes
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N Neubauer, RN Kulkarni |
ILAR journal / National Research Council, Institute of Laboratory Animal Resources | 2006 |
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HJ HAN, SH PARK |
Journal of Veterinary Medical Science | 2006 |
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P Alonso-Magdalena, S Morimoto, C Ripoll, E Fuentes, A Nadal |
Environmental Health Perspectives | 2005 |
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DJ Hill |
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New insights into the roles of insulin/IGF-I in the development and maintenance of beta-cell mass
RN Kulkarni |
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Cell Engineering
M Al-Rubeai, M Fussenegger |
2005 | |
Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia
M Bohlooly-Y, M Bohlooly, B Olsson, CE Bruder, D Lindén, K Sjögren, M Bjursell, E Egecioglu, L Svensson, P Brodin, JC Waterton, OG Isaksson, F Sundler, B Ahrén, C Ohlsson, J Oscarsson, J Törnell |
Diabetes | 2004 |
Pancreatic-specific inactivation of IGF-I gene causes enlarged pancreatic islets and significant resistance to diabetes
Y Lu, PL Herrera, Y Guo, D Sun, Z Tang, D LeRoith, JL Liu |
Diabetes | 2004 |
Mouse Models of Insulin Resistance
A NANDI |
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Gastroenterology | 2004 |
Insulin-like growth factors and pancreas beta cells
TW van Haeften, TB Twickler |
European Journal of Clinical Investigation | 2004 |
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MJ Dunne, KE Cosgrove, RM Shepherd, A Aynsley-Green, KJ Lindley |
Physiological reviews | 2004 |
IGF and Nutrition in Health and Disease
MS Houston, JM Holly, EL Feldman |
2004 | |
Transplantation of the Pancreas
RW Gruessner, DE Sutherland |
2004 | |
International Textbook of Diabetes Mellitus
RA DeFronzo, L Mandarino, E Ferrannini |
International Textbook of Diabetes Mellitus | 2003 |
Biology of insulin-like growth factors in development
J Dupont, M Holzenberger |
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Insulin-like growth factor II and its receptors in atherosclerosis and in conditions predisposing to atherosclerosis
S Zaina, J Nilsson |
Current Opinion in Lipidology | 2003 |
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HY Wong, B Ahrén, CJ Lips, JW Höppener, F Sundler |
Regulatory Peptides | 2003 |
Glucose transporter-1-deficient mice exhibit impaired development and deformities that are similar to diabetic embryopathy
CW Heilig, T Saunders, FC 3rd, K Moley, K Heilig, R Baggs, LR Guo, D Conner |
Proceedings of the National Academy of Sciences | 2003 |
The focal form of persistent hyperinsulinemic hypoglycemia of infancy: morphological and molecular studies show structural and functional differences with insulinoma
Christine Sempoux, Yves Guiot, Karin Dahan, Pierre Moulin, Martine Stevens, Virginie Lambot, Pascale de Lonlay, Jean-Christophe Fournet, Claudine Junien, Francis Jaubert, Claire Nihoul-Fekete, Jean-Marie Saudubray, Jacques Rahier |
Diabetes | 2003 |
ß-cell expression of insulin-like growth factor-I leads to recovery from type 1 diabetes
Mónica George, Eduard Ayuso, Alba Casellas, Cristina Costa, Jean Christophe Devedjian, Fatima Bosch |
Journal of Clinical Investigation | 2002 |
Defective insulin secretion in pancreatic beta cells lacking type 1 IGF receptor
Shouhong Xuan, Tadahiro Kitamura, Jun Nakae, Katerina Politi, Yoshiaki Kido, Peter E. Fisher, Manrico Morroni, Saverio Cinti, Morris F. White, Pedro L. Herrera, Domenico Accili and Argiris Efstratiadis |
Journal of Clinical Investigation | 2002 |
Pancreatic β-cell growth and survival – a role in obesity-linked type 2 diabetes?
MK Lingohr, R Buettner, CJ Rhodes |
Trends in Molecular Medicine | 2002 |
Islet hyperplasia in callitrichids
C Juan-Sallés, A Marco, JA Ramos-Vara, A Resendes, J Vergés, X Valls, A Montesinos |
Primates | 2002 |
Diethylnitrosamine induces long-lasting re-expression of insulin-like growth factor II during early stages of liver carcinogenesis in mice
H Lahm, K Gittner, O Krebs, L Sprague, E Deml, D Oesterle, A Hoeflich, R Wanke, E Wolf |
Growth Hormone & IGF Research | 2002 |
Hepatocyte Nuclear Factor-1 Modulates Pancreatic -Cell Growth by Regulating the Expression of Insulin-Like Growth Factor-1 in INS-1 Cells
Q Yang, K Yamagata, K Fukui, Y Cao, T Nammo, H Iwahashi, H Wang, I Matsumura, T Hanafusa, R Bucala, CB Wollheim, J Miyagawa, Y Matsuzawa |
Diabetes | 2002 |
Fetal Insulin-Like Growth Factor-2 Production Is Impaired in the GK Rat Model of Type 2 Diabetes
P Serradas, L Goya, M Lacorne, MN Gangnerau, S Ramos, C Alvarez, AM Pascual-Leone, B Portha |
Diabetes | 2002 |
Adenovirus-mediated Hepatocyte Growth Factor Expression in Mouse Islets Improves Pancreatic Islet Transplant Performance and Reduces Beta Cell Death
A Garcı́a-Ocaña, KK Takane, VT Reddy, JC Lopez-Talavera, RC Vasavada, AF Stewart |
The Journal of biological chemistry | 2002 |
Diabetes and insulin secretion: whither K ATP ?
CG Nichols, JC Koster |
American journal of physiology. Endocrinology and metabolism | 2002 |
Transgenic mice expressing a constitutively active Akt1/PKBalpha in pancreatic islet beta-cells exhibit striking hypertrophy, hyperplasia, and hyperinsulinemia
Ernesto Bernal-Mizrachi, Wu Wen, Sarah Stahlhut, Cris M. Welling, M. Alan Permutt |
Journal of Clinical Investigation | 2001 |
Transgenic overexpression of hepatocyte growth factor in the beta-cell markedly improves islet function and islet transplant outcomes in mice
A García-Ocaña, RC Vasavada, A Cebrian, V Reddy, KK Takane, JC López-Talavera, AF Stewart |
Diabetes | 2001 |
The use of transgenic mice in pharmacokinetic and pharmacodynamic studies
WF Elmquist, DW Miller |
Journal of Pharmaceutical Sciences | 2001 |
A compendium of gene expression in normal human tissues
LL Hsiao, F Dangond, T Yoshida, R Hong, RV Jensen, J Misra, W Dillon, KF Lee, KE Clark, P Haverty, Z Weng, GL Mutter, MP Frosch, MA MacDONALD, EL Milford, CP Crum, R Bueno, RE Pratt, M Mahadevappa, JA Warrington, G Stephanopoulos, G Stephanopoulos, SR Gullans |
Physiological genomics | 2001 |
Molecular Basis of Pancreas Development and Function
JF Habener, MA Hussain |
2001 |