Adiposity-Independent Effects of Aging on Insulin Sensitivity and Clearance in Mice and Humans
Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes
Cellular and Molecular Physiology | Endocrinology | Hormones, Hormone Substitutes, and Hormone Antagonists | Lipids | Nutritional and Metabolic Diseases
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.
DOI of Published Version
Obesity (Silver Spring). 2019 Mar;27(3):434-443. doi: 10.1002/oby.22418. Link to article on publisher's site
Obesity (Silver Spring, Md.)
Ehrhardt, Nicole; Cui, Jinrui; Dagdeviren, Sezin; Saengnipanthkul, Suchaorn; Goodridge, Helen S.; Kim, Jason K.; Lantier, Louise; Guo, Xiuqing; Chen, Yii-Der I.; Raffel, Leslie J.; Buchanan, Thomas A.; Hsueh, Willa A.; Rotter, Jerome I.; Goodarzi, Mark O.; and Peterfy, Miklos, "Adiposity-Independent Effects of Aging on Insulin Sensitivity and Clearance in Mice and Humans" (2019). Program in Molecular Medicine Publications and Presentations. 118.