Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-36289-0
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Funding
- NIA Aging Rodent Colony
- NIH [AG050135, AG062328, DK102598, AG041765, AG051974, AG056771, DK101683, DK113103]
- American Diabetes Association [1-16-IBS-212]
- Wisconsin Partnership Program
- Central Society for Clinical and Translational Research
- Glenn Foundation Award for Research in the Biological Mechanisms of Aging
- American Federation for Aging Research
- UW Biotechnology Training Program [T32GM008349]
- American Diabetes Association
- UW Institute on Aging [NIA T32 AG000213]
- U.S. Department of Veterans Affairs [I01-BX004031]
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK113103, K01DK101683] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R21AG051974, R01AG056771, T32AG000213, R00AG041765, R21AG050135] Funding Source: NIH RePORTER
- Veterans Affairs [I01BX004031] Funding Source: NIH RePORTER
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Type 2 diabetes is an age-and-obesity associated disease driven by impairments in glucose homeostasis that ultimately result in defective insulin secretion from pancreatic beta-cells. To deconvolve the effects of age and obesity in an experimental model of prediabetes, we fed young and aged mice either chow or a short-term high-fat/high-sucrose Western diet (WD) and examined how weight, glucose tolerance, and beta-cell function were affected. Although WD induced a similar degree of weight gain in young and aged mice, a high degree of heterogeneity was found exclusively in aged mice. Weight gain in WD-fed aged mice was well-correlated with glucose intolerance, fasting insulin, and in vivo glucose-stimulated insulin secretion, relationships that were not observed in young animals. Although beta-cell mass expansion in the WD-fed aged mice was only three-quarters of that observed in young mice, the islets from aged mice were resistant to the sharp WD-induced decline in ex vivo insulin secretion observed in young mice. Our findings demonstrate that age is associated with the protection of islet function in diet-induced obese mice, and furthermore, that WD challenge exposes variability in the resilience of the insulin secretory pathway in aged mice.
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