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

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Abstract

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 Vmax and Km values for adipocyte glucose transport were calculated from the 2-deoxy glucose uptake data. The results demonstrated that in cells from control animals the Vmax 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 Vmax 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, 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 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 Vmax, with increased Vmax values in hyperinsulinemic rats and decreased Vmax 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) Vmax values. The apparent Km for 2-deoxy glucose uptake was the same under all conditions.

Authors

Masashi Kobayashi, Jerrold M. Olefsky