Age-Dependent Protection of Insulin Secretion in Diet Induced Obese Mice

Sci Rep. 2018 Dec 13;8(1):17814. doi: 10.1038/s41598-018-36289-0.


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 β-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 β-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 β-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aging / metabolism*
  • Aging / pathology
  • Animals
  • Diet, Western / adverse effects*
  • Glucose Intolerance / etiology
  • Glucose Intolerance / metabolism*
  • Glucose Intolerance / pathology
  • Glucose Intolerance / prevention & control
  • Insulin / metabolism*
  • Insulin Secretion*
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Male
  • Mice
  • Obesity / etiology
  • Obesity / metabolism*
  • Obesity / pathology
  • Obesity / prevention & control


  • Insulin