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Mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes

Dion, François; Dumayne, Christopher; Henley, Nathalie; Beauchemin, Stéphanie; Arias, Edward B.; Leblond, François A.; Lesage, Sylvie; Lefrancois, Stéphane; Cartee, Gregory D.; Pichette, Vincent (2017). Mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes PLoS One , vol. 12 , nº 5. e0176650-1-17. DOI: 10.1371/journal.pone.0176650.

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Résumé

Chronic kidney disease is associated with homeostatic imbalances such as insulin resistance. However, the underlying mechanisms leading to these imbalances and whether they promote the development of type 2 diabetes is unknown. The effect of chronic kidney disease on insulin resistance was studied on two different rat strains. First, in a 5/6th nephrectomised Sprague-Dawley rat model of chronic kidney disease, we observed a correlation between the severity of chronic kidney disease and hyperglycemia as evaluated by serum fructosamine levels (p≺0.0001). Further, glucose tolerance tests indicated an increase of 25% in glycemia in chronic kidney disease rats (p≺0.0001) as compared to controls whereas insulin levels remained unchanged. We also observed modulation of glucose transporters expression in several tissues such as the liver (decrease of approximately 40%, p≺/=0.01) and muscles (decrease of approximately 29%, p≺/=0.05). Despite a significant reduction of approximately 37% in insulin-dependent glucose uptake in the muscles of chronic kidney disease rats (p≺0.0001), the development of type 2 diabetes was never observed. Second, in a rat model of metabolic syndrome (Zucker Leprfa/fa), chronic kidney disease caused a 50% increased fasting hyperglycemia (p≺0.0001) and an exacerbated glycemic response (p≺0.0001) during glucose challenge. Similar modulations of glucose transporters expression and glucose uptake were observed in the two models. However, 30% (p≺0.05) of chronic kidney disease Zucker rats developed characteristics of type 2 diabetes. Thus, our results suggest that downregulation of GLUT4 in skeletal muscle may be associated with insulin resistance in chronic kidney disease and could lead to type 2 diabetes in predisposed animals.

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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 25 juin 2017 18:11
Dernière modification: 25 juin 2017 18:11
URI: http://espace.inrs.ca/id/eprint/5348

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