Long-Term Regulation of Adipocyte Glucose Transport Capacity by Circulating Insulin in Rats

Masashi Kobayashi; Jerrold M. Olefsky

doi:10.1172/JCI109116

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). The mean (±SE) 9 a.m. plasma insulin level for each experimental group was: hyperinsulinemic animals, 65±5 μU/ml; controls, 32±3 μU/ml; low dose streptozotocin group, 18±3 μU/ml; and high dose streptozotocin group 5±2 μU/ml. 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. The V_max and K_m values for adipocyte glucose transport were calculated from the 2-deoxy glucose uptake data. The results demonstrated that in cells from control animals the V_max of in vitro adipocyte glucose transport was 7.1±0.7 nmol/min per 10⁶ cells in the basal state and 22.9±0.9 nmol/min per 10⁶ cells in the presence of a maximally effective insulin concentration (25 ng/ml) in the buffer. In cells from the experimentally hyperinsulinemic animals these V_max values were increased to 11.7±0.8 and 44.2±1.1 nmol/min per 10⁶ cells. Using adipocytes from both groups of streptozotocin-treated (high dose, 55 mg/kg; low dose, 40 mg/kg) insulin-deficient diabetic animals, V_max values were found to be progressively decreased. Thus, in the low dose group, basal-and insulin-stimulated V_max values were 1.6±0.5 and 5.7±0.7 nmol/min per 10⁶ cells, as compared to values of 0.9±0.2 and 1.7±0.6 in the high dose group. Thus, when considered as group data a positive relationship was found between circulating plasma insulin levels and adipocyte glucose transport V_max, with increased V_max values in hyperinsulinemic rats and decreased V_max values in hypoinsulinemic rats. Furthermore, when the individual data were analyzed, highly significant correlation coefficients were found between the height of the plasma insulin level and both the basal (r = 0.82, P < 0.001) and insulin-stimulated (r = 0.93, P < 0.001) V_max values. The apparent K_m for 2-deoxy glucose uptake was the same under all conditions.

In conclusion, assuming that the V_max 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.