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Adiposity-Independent Effects of Aging on Insulin Sensitivity and Clearance in
Mice and Humans.
Authors Ehrhardt N, Cui J, Dagdeviren S, Saengnipanthkul S, Goodridge HS, Kim JK,
Lantier L, Guo X, Chen YI, Raffel LJ, Buchanan TA, Hsueh WA, Rotter JI, Goodarzi
MO, Péterfy M
Submitted By Submitted Externally on 2/28/2019
Status Published
Journal Obesity (Silver Spring, Md.)
Year 2019
Date Published 3/1/2019
Volume : Pages 27 : 434 - 443
PubMed Reference 30801985
Abstract 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., 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., 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., This study demonstrates that in addition
to altered body composition, adiposity-independent mechanisms also contribute to
aging-associated insulin resistance in mice and humans.


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