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Obesity (Silver Spring). 2019 Mar;27(3):434-443. doi: 10.1002/oby.22418.

Adiposity-Independent Effects of Aging on Insulin Sensitivity and Clearance in Mice and Humans.

Author information

1
Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, California, USA.
2
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
3
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
4
Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
5
Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
6
Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
7
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.
8
Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, California, USA.
9
Department of Pediatrics, Division of Genetic and Genomic Medicine, University of California, Irvine, California, USA.
10
Department of Physiology and Biophysics and Department of Medicine, Keck School of Medicine of USC, Los Angeles, California, USA.
11
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA.
12
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

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.

PMID:
30801985
PMCID:
PMC6474357
[Available on 2020-03-01]
DOI:
10.1002/oby.22418

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