Insulin action on adipocytes. Evidence that the anti-lipolytic and lipogenic effects of insulin are mediated by the same receptor

Abstract

1. The dose-response relationships of insulin stimulation of lipogenesis and inhibition of lipolysis were studied simultaneously by using rat adipocytes to determine whether these different effects of insulin are mediated through the same or different sets of receptors. 2. The sensitivity (defined as the concentration of insulin required to produce a half-maximal effect) of the stimulated lipogenic response to insulin was not significantly different from the sensitivity of the anti-lipolytic response to insulin. The addition of different adrenaline and glucose concentrations did not alter the half-maximal concentration of insulin required to inhibit lipolysis. 3. The specificities of the lipogenic and antilipolytic responses were studied by using insulin analogues. The sensitivities of the lipogenic and anti-lipolytic responses were the same for five chemically modified insulins and hagfish insulin, which have potencies compared with bovine insulin of between 3 and 90%. 4. Starving rats for 48h significantly increased the sensitivities of both the antilipolytic and lipogenic responses to insulin, but the changes in the sensitivities of both lipogenesis and anti-lipolysis returned to that of fed rats. 5. We conclude that insulin stimulates lipogenesis and inhibits lipolysis over the same concentration range. These observations provide powerful evidence that the different effects of insulin are mediated through the same set of receptors.

Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathway

“…Previous studies with rat fat cells suggested that the degree of antilipolysis induced by insulin depends on the rate of lipolysis before the addition of insulin [25]. Thus, the antilipolytic effect of insulin is more pronounced in rodent adipose tissue when lipolysis is raised.…”

Fat accumulation in the rat during early pregnancy is modulated by enhanced insulin responsiveness

“…This higher antilipolytic action of insulin in early gestation should play a very important role in the maintenance of fat deposition. Previous studies with rat fat cells have hypothesized that the degree of antilipolysis induced by insulin depends on the rate of lipolysis before the addition of the hormone (56). Thus the antilipolytic effect is more pronounced when the lipolysis is raised.…”

“…Furthermore, because the ␤-adrenoceptor activity is impaired when nonpregnant animals become hyperinsulinemic by means of the euglycemic hyperinsulinemic clamp (23), we can speculate that the lower catecholamine-stimulated lipolysis in late gestation could be a consequence of decreased adrenoceptor activity secondary to maternal hyperinsulinemia. The antilipolytic effect of insulin is considered the most sensitive of its metabolic actions (56), so it requires a much lower insulin concentration (1 nM in our study) than other response sites like the stimulation of glucose transport (Ͼ10 nM for glucose uptake and lipogenesis). Hence, even in insulin resistance states, in which glucose transport is impaired, sensitivity to insulin's antilipolytic effect is relatively preserved.…”

Insulin, growth hormone and sport

“…This is most easily shown in isolated adipocytes from young rats and is illustrated in Fig. 1 (Thomas et al 1979). What the 1950s biochemists failed to take notice of was the considerable uptake of glucose that takes place in all tissues even when insulin is absent.…”