A note on ‘aging-pharmacodynamics’ with application to the analysis of the age-dynamics of adipocyte response to epinephrine and insulin

The Aging Fat Cell

“…Progressive desensitization of the adipocyte to insulin stimulation worsens this effect. This is in line with the overall impairment in glucose tolerance observed in elderly human and laboratory animals, which is partially explained by the development of peripheral tissue insulin‐resistance 220,227–229 …”

“…Insulin presents an antilipolytic effect that seems to decrease with age 254,269 . However, the sensitivity of rat adipocytes to the antilipolytic action of insulin at moderate epinephrine concentrations in the incubation medium appeared to decrease during maturation but then to increase at very old age, recalling the rebound effect noted in catecholamine sensitivity 104,229,270 . On the other hand, the antilipolytic effect of prostaglandin E2, mediated through an inhibition of the adenylate cyclase complex, was found to be unchanged in elderly humans compared to young ones 271 …”

“…Moreover, on the basis of fat cell size, a number of conflicting results have been obtained. In some studies, higher rates of stimulated lipolysis were found in large adipocytes than in small ones, 104,229 whereas in other studies, no differences were detected between large and small adipocytes 254,255 . Fatcell size, as well as the mode of expression of the results, has to be carefully taken into account when attempting to analyze the lipolytic responses.…”

“…On the other hand, a negative correlation between adipocyte sensitivity to epinephrine and adipocyte volume has been described 104 . As the evolution of fat‐cell size with age may be biphasic, presenting an increase in volume during maturation and a decrease in senescence, this may explain the rebound effect (decrease at maturity followed by increase at old age) in epinephrine‐sensitivity that has been noted in some studies 229 …”