Ability of circulating insulin to chronically regulate the cellular glucose transport system.

We have tested the idea that the circulating plasma insulin level plays an important role in the long-term regulation, or maintenance, of the cellular glucose transport system, distinct from insulin's ability to acutely accelerate glucose transport. To study this hypothesis, groups of rats were made either hyperinsulinemic or hypoinsulinemic by daily insulin injections or Streptozotocin treatment, respectively. Different levels of hypoinsulinemia were produced by using different doses of Streptozotocin (40 and 55 mg/kg). Isolated adipocytes were prepared from each animal and glucose transport was assessed by measuring the initial rates of uptake of the nonmetabolyzable hexose 2-deoxy glucose. In cells from control animals, the Vmax of in vitro adipocyte glucose transport was 7.1 +/- 0.7 nmole/min/10(6) cells in the basal state and 22.9 +/- 0.9 nmole/min/10(6) cells in the presence of a maximally effective insulin concentration (25 ng/ml) in the buffer. In cells from the experimentally hyperinsulinemic animals, these Vmax values were increased to 11.7 +/- 0.8 and 44.2 +/- 1.1 nmole/min/10(6) cells. Using adipocytes from both groups of Streptozotocin treated (high dose, 55 mg/kg, low dose, 40 mg/kg) insulin deficient diabetic animals, Vmax values were found to be progressively decreased. Thus, in the low dose group, basal and insulin stimulated Vmax values were 1.6 +/- 0.5 and 5.7 +/- 0.7 nmole/min/10(6) cells, as compared to values of 0.9 +/- 0.2 and 1.7 +/- 0.6 in the high dose group. Furthermore, when hyperinsulinemia was induced by feeding rats high carbohydrate diets for 10 days, adipocyte glucose transport Vmax increased 50%. In contrast, when hypoinsulinemia was achieved by fasting rats for 72 hr, transport Vmax decreased by 50%. The apparent Km for 2-deoxy glucose uptake was the same under all conditions. In conclusion, assuming that the Vmax of transport is some function of the number of glucose transport carriers per cell, then these results support the hypothesis that in addition to acute acceleration of glucose transport, insulin is also an important long-term regulator of the number of available adipocyte glucose transport carriers.