Mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes.
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 o...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5411038?pdf=render |
| _version_ | 1818448307592101888 |
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| author | François Dion Christopher Dumayne Nathalie Henley Stéphanie Beauchemin Edward B Arias François A Leblond Sylvie Lesage Stéphane Lefrançois Gregory D Cartee Vincent Pichette |
| author_facet | François Dion Christopher Dumayne Nathalie Henley Stéphanie Beauchemin Edward B Arias François A Leblond Sylvie Lesage Stéphane Lefrançois Gregory D Cartee Vincent Pichette |
| author_sort | François Dion |
| collection | DOAJ |
| description | 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 ≈40%, p≤0.01) and muscles (decrease of ≈29%, p≤0.05). Despite a significant reduction of ≈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. |
| first_indexed | 2024-12-14T20:17:26Z |
| format | Article |
| id | doaj.art-79b1025840744f66b9ade14bde48b4d5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T20:17:26Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-79b1025840744f66b9ade14bde48b4d52022-12-21T22:48:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01125e017665010.1371/journal.pone.0176650Mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes.François DionChristopher DumayneNathalie HenleyStéphanie BeaucheminEdward B AriasFrançois A LeblondSylvie LesageStéphane LefrançoisGregory D CarteeVincent PichetteChronic 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 ≈40%, p≤0.01) and muscles (decrease of ≈29%, p≤0.05). Despite a significant reduction of ≈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.http://europepmc.org/articles/PMC5411038?pdf=render |
| spellingShingle | François Dion Christopher Dumayne Nathalie Henley Stéphanie Beauchemin Edward B Arias François A Leblond Sylvie Lesage Stéphane Lefrançois Gregory D Cartee Vincent Pichette Mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes. PLoS ONE |
| title | Mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes. |
| title_full | Mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes. |
| title_fullStr | Mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes. |
| title_full_unstemmed | Mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes. |
| title_short | Mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes. |
| title_sort | mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes |
| url | http://europepmc.org/articles/PMC5411038?pdf=render |
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