Short-term physical exercise controls age-related hyperinsulinemia and improves hepatic metabolism in aged rodents

J Endocrinol Invest. 2023 Apr;46(4):815-827. doi: 10.1007/s40618-022-01947-8. Epub 2022 Nov 1.

Abstract

Purpose: Aging is associated with changes in glucose homeostasis related to both decreased insulin secretion and/or impaired insulin action, contributing to the high prevalence of type 2 diabetes (T2D) in the elderly population. Additionally, studies are showing that chronically high levels of circulating insulin can also lead to insulin resistance. In contrast, physical exercise has been a strategy used to improve insulin sensitivity and metabolic health. However, the molecular alterations resulting from the effects of physical exercise in the liver on age-related hyperinsulinemia conditions are not yet fully established. This study aimed to investigate the effects of 7 days of aerobic exercise on hepatic metabolism in aged hyperinsulinemic rats (i.e., Wistar and F344) and in Slc2a4+/- mice (hyperglycemic and hyperinsulinemic mice).

Results: Both aged models showed alterations in insulin and glucose tolerance, which were associated with essential changes in hepatic fat metabolism (lipogenesis, gluconeogenesis, and inflammation). In contrast, 7 days of physical exercise was efficient in improving whole-body glucose and insulin sensitivity, and hepatic metabolism. The Slc2a4+/- mice presented significant metabolic impairments (insulin resistance and hepatic fat accumulation) that were improved by short-term exercise training. In this scenario, high circulating insulin may be an important contributor to age-related insulin resistance and hepatic disarrangements in some specific conditions.

Conclusion: In conclusion, our data demonstrated that short-term aerobic exercise was able to control mechanisms related to hepatic fat accumulation and insulin sensitivity in aged rodents. These effects could contribute to late-life metabolic health and prevent the development/progression of age-related T2D.

Keywords: Aging; Hyperinsulinemia; Liver; Physical exercise.

MeSH terms

  • Aged
  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2* / metabolism
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Liver / metabolism
  • Mice
  • Physical Conditioning, Animal
  • Rats
  • Rats, Inbred F344
  • Rats, Wistar
  • Rodentia / metabolism

Substances

  • Blood Glucose
  • Glucose
  • Insulin