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Abstract

The Goto-Kakisaki (GK) rat is a genetic model of non-insulin-dependent diabetes. At 21.5 d of age we found that GK fetuses had an increased plasma glucose concentration, a decreased plasma insulin level, and a reduced pancreatic beta cell mass. To investigate the beta cell function during fetal life we used a hyperglycemic clamp protocol applied to the mothers, which allowed us to obtain a steady-state hyperglycemia in the corresponding fetuses. At variance, with Wistar (W) fetuses, plasma insulin concentration in GK fetuses did not rise in response to hyperglycemia. In contrast, GK fetal pancreas released insulin in response to glucose in vitro to the same extent as W fetal pancreas. Such a discrepancy between the in vivo and in vitro results suggests that the lack of pancreatic reactivity to glucose as seen in vivo is extrinsic to the fetal GK beta cell. Finally, the importance of gestational hyperglycemia was investigated by performing crosses between GK and W rats. Fetuses issued from crosses between W mother and GK father or GK mother and W father had a beta cell mass close to normal values and were still able to increase their plasma insulin levels in response to hyperglycemia in vivo. Our data suggest that hyperglycemia in utero does not influence the severity of the decrease of the beta cell mass or the lack of the insulin secretory response to glucose in the fetal GK rat. Moreover they indicate that conjunction of GK genes originating from both parents is necessary in order for these defects to be fully expressed.

Authors

P Serradas, M N Gangnerau, M H Giroix, C Saulnier, B Portha

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Total citations by year

Year: 2014 2013 2012 2011 2008 2007 2006 2005 2003 2000 1999 Total
Citations: 1 5 2 3 1 1 3 1 2 2 2 23
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Citations to this article (23)

Title and authors Publication Year
Maternal diabetes, programming of beta-cell disorders and intergenerational risk of type 2 diabetes
A Chavey, MD Kioon, D Bailbé, J Movassat, B Portha
Diabetes & Metabolism 2014
Maternal rat diabetes mellitus deleteriously affects insulin sensitivity and Beta-cell function in the offspring
AB Aref, OM Ahmed, LA Ali, M Semmler
Journal of Diabetes Research 2013
Remodelling of the intracardiac ganglia in diabetic Goto-Kakizaki rats: an anatomical study
D Batulevicius, T Frese, E Peschke, DH Pauza, V Batuleviciene
Cardiovascular Diabetology 2013
Effects of polysaccharide from pumpkin on biochemical indicator and pancreatic tissue of the diabetic rabbits
Y Zhang, P Chen, Y Zhang, H Jin, L Zhu, J Li, H Yao
International Journal of Biological Macromolecules 2013
Studies on the extraction of pumpkin components and their biological effects on blood glucose of diabetic mice
H Jin, YJ Zhang, JX Jiang, LY Zhu, P Chen, J Li, HY Yao
Journal of Food and Drug Analysis 2013
Remodelling of the intracardiac ganglia in diabetic Goto-Kakizaki rats: an anatomical study
D Batulevicius, T Frese, E Peschke, DH Pauza, V Batuleviciene
Cardiovascular Diabetology 2013
A euglycaemic/non-diabetic perinatal environment does not alleviate early beta cell maldevelopment and type 2 diabetes risk in the GK/Par rat model
A Chavey, D Bailbé, L Maulny, JP Renard, J Movassat, B Portha
Diabetologia 2012
Severe Maternal Hyperglycemia Exacerbates the Development of Insulin Resistance and Fatty Liver in the Offspring on High Fat Diet
Y Song, J Li, Y Zhao, Q Zhang, Z Liu, J Li, X Chen, Z Yang, C Yu, X Xiao
Experimental Diabetes Research 2012
Early-Life Origins of Type 2 Diabetes: Fetal Programming of the Beta-Cell Mass
B Portha, A Chavey, J Movassat
Experimental Diabetes Research 2011
Long-term fenofibrate treatment impaired glucose-stimulated insulin secretion and up-regulated pancreatic NF-kappa B and iNOS expression in monosodium glutamate-induced obese rats: Is that a latent disadvantage?
S Liu, Q Liu, L Li, Y Huan, S Sun, Z Shen
Journal of Translational Medicine 2011
Hypercholesterolaemia, signs of islet microangiopathy and altered angiogenesis precede onset of type 2 diabetes in the Goto–Kakizaki (GK) rat
MH Giroix, JC Irminger, G Lacraz, C Noll, S Calderari, JA Ehses, J Coulaud, M Cornut, N Kassis, F Schmidlin, JL Paul, M Kergoat, N Janel, PA Halban, F Homo-Delarche
Diabetologia 2011
Decreased fetal size is associated with beta-cell hyperfunction in early life and failure with age
MV Chakravarthy, Y Zhu, MB Wice, T Coleman, KL Pappan, CA Marshall, ML McDaniel, CF Semenkovich
Diabetes 2008
Defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly in the Goto–Kakizaki rat model of type 2 diabetes
S Calderari, MN Gangnerau, M Thibault, MJ Meile, N Kassis, C Alvarez, B Portha, P Serradas
Diabetologia 2007
Effects of hyperglycemia on sperm and testicular cells of Goto-Kakizaki and streptozotocin-treated rat models for diabetes
S Amaral, AJ Moreno, MS Santos, R Seiça, J Ramalho-Santos
Theriogenology 2006
Is Defective Pancreatic Beta-cell Mass Environmentally Programmed in Goto-Kakizaki Rat Model of Type 2 Diabetes?
S Calderari, MN Gangnerau, MJ Meile, B Portha, P Serradas
Pancreas 2006
Animal models of type 2 diabetes with reduced pancreatic β-cell mass
P Masiello
The International Journal of Biochemistry & Cell Biology 2006
Programmed disorders of β-cell development and function as one cause for type 2 diabetes? The GK rat paradigm
B Portha
Diabetes/Metabolism Research and Reviews 2005
Diabetes and mitochondrial bioenergetics: Alterations with age
FM Ferreira, CM Palmeira, R Sei�a, AJ Moreno, MS Santos
Journal of Biochemical and Molecular Toxicology 2003
Lifetime consequences of abnormal fetal pancreatic development
K Holemans, L Aerts, FA van Assche
The Journal of Physiology 2003
Susceptibility to β-Amyloid-Induced Toxicity Is Decreased in Goto-Kakizaki Diabetic Rats: Involvement of Oxidative Stress
C Pereira, P Moreira, R Seiça, MS Santos, CR Oliveira
Experimental Neurology 2000
Genetics of Type 2 Diabetes: An Overview for the Millennium
SC Elbein
Diabetes Technology & Therapeutics 2000
Alterations of liver mitochondrial bioenergetics in diabetic Goto-Kakizaki rats
FM Ferreira, CM Palmeira, R Seiça, MS Santos
Metabolism 1999
Decreased susceptibility to lipid peroxidation of Goto-Kakizaki rats: Relationship to mitochondrial antioxidant capacity
FM Ferreira, CM Palmeira, MJ Matos, R Seiça, MS Santos
Life Sciences 1999

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