Insulin sensitization by voluntary exercise in aging rats is mediated through hepatic insulin sensitizing substance (HISS)

BackgroundFood in the upper gastrointestinal tract potentiates the glucose uptake response to insulin. Meal-induced insulin sensitization (MIS) occurs as a result of insulin-mediated release of hepatic insulin sensitizing substance (HISS) that increases glucose uptake in peripheral tissues. HISS release decreases with age, and exercise causes metabolic improvements in aging, therefore it is important to analyze the effect of exercise on age-associated decline in HISS-action.ObjectivesThe aim of this study is to test the hypothesis that improved insulin sensitivity, by voluntary running-wheel exercise in aging rats, is attained by preserving the HISS response. We also investigate the possible association of exercise-mediated beneficial changes in metabolic conditions and body composition with improved HISS-action.MethodsWe measured insulin- and HISS-sensitivity in 9, 14 and 21-week old rats with/without exercise. Metabolic markers were also determined in age-matched control and exercised rats.ResultsExercise significantly improved HISS-dependent glucose uptake in all age groups. The direct action of insulin was minimally altered by age or exercise. Body composition and metabolic conditions were beneficially changed with exercise-induced improvements in the HISS response.ConclusionThe therapeutic efficacy of voluntary exercise against insulin resistance in aging rats is achieved mainly through restoration of HISS-action.

Research highlights
► Food in the upper GIT potentiates the glucose uptake response to insulin.
► This occurs through the release of hepatic insulin sensitizing substance (HISS).
► HISS-action is impaired with age, and causes postprandial metabolic abnormalities.
► 7-day voluntary running-wheel exercise restored HISS-action in aging rats.
► Improved HISS-action by exercise in aging rendered multiple metabolic benefits.