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Adiposity-Independent Effects of Aging on Insulin Sensitivity and Clearance in Mice and Humans.
Citation | “Adiposity-Independent Effects Of Aging On Insulin Sensitivity And Clearance In Mice And Humans.”. Obesity (Silver Spring, Md.), pp. 434-443. . |
Center | Vanderbilt University UCSD-UCLA |
Multicenter |
Multicenter
|
Author | Nicole Ehrhardt, Jinrui Cui, Sezin Dagdeviren, Suchaorn Saengnipanthkul, Helen S Goodridge, Jason K Kim, Louise Lantier, Xiuqing Guo, Yii-Der I Chen, Leslie J Raffel, Thomas A Buchanan, Willa A Hsueh, Jerome I Rotter, Mark O Goodarzi, Miklós Péterfy |
Abstract |
OBJECTIVE: Aging is associated with impaired insulin sensitivity and increased prevalence of type 2 diabetes. However, it remains unclear whether aging-associated insulin resistance is due to increased adiposity or other age-related factors. To address this question, the impact of aging on insulin sensitivity was investigated independently of changes in body composition. METHODS: Cohorts of mice aged 4 to 8 months ("young") and 18 to 27 months ("aged") exhibiting similar body composition were characterized for glucose metabolism on chow and high-fat diets. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp analyses. The relationship between aging and insulin resistance in humans was investigated in 1,250 nondiabetic Mexican Americans who underwent hyperinsulinemic-euglycemic clamps. RESULTS: In mice with similar body composition, age had no detrimental effect on plasma glucose and insulin levels. While aging did not diminish glucose tolerance, hyperinsulinemic-euglycemic clamps demonstrated impaired insulin sensitivity and reduced insulin clearance in aged mice on chow and high-fat diets. Consistent with results in the mouse, age remained an independent determinant of insulin resistance after adjustment for body composition in Mexican American males. CONCLUSIONS: This study demonstrates that in addition to altered body composition, adiposity-independent mechanisms also contribute to aging-associated insulin resistance in mice and humans. |
Year of Publication |
2019
|
Journal |
Obesity (Silver Spring, Md.)
|
Volume |
27
|
Issue |
3
|
Number of Pages |
434-443
|
Date Published |
12/2019
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ISSN Number |
1930-739X
|
DOI |
10.1002/oby.22418
|
Alternate Journal |
Obesity (Silver Spring)
|
PMID |
30801985
|
PMCID |
PMC6474357
|
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