Reversal of Insulin Resistance in Diabetic Rat Adipocytes by Insulin Therapy: Restoration of Pool of Glucose Transporters and Enhancement of Glucose-Transport Activity
To determine the role of insulin in reversing the insulin resistance associated with depletion of the intracellular pool of glucose transporters, streptozocin-induced diabetic rats were treated with 5 U/day s.c. of insulin for 0, 8, or 14 days. At each time point, adipose cells were isolated, and 3-O-methylglucose transport was measured in the absence and presence of 1000 μU/ml insulin. With the cytochalasin B-binding assay, concentrations of glucose transporters in the plasma and the low-density microsomal membrane fractions were determined. Eight-day insulin therapy enhanced glucose transport rate (mean ± SE) from 0.2 ± 0.0 to 1.1 ± 0.1 fmol · cell−1 · min−1 in the basal state and from 0.8 ± 0.1 to 5.5 ± 0.4 fmol · cell−1 · min−1 in the insulin-stimulated state in untreated and treated diabetic rats, respectively; this is a 3-fold increment of glucose transport rate in both states compared with control rats. After 14-day insulin therapy, glucose-transport activity declined toward normal but still remained ∼1.5- and 4-fold higher than control and diabetic rats, respectively. Despite the persistent enhancement of glucose transport rate, concentration of glucose transporters in the intracellular pool was restored only to its prediabetic state. Likewise, the increased concentration of glucose transporters in the plasma membranes after insulin stimulation was similar to that of control rats. Thus, we suggest that 8–14 days of insulin therapy reversed the insulin resistance in diabetic rat adipocytes by at least two mechanisms: restoration of the intracellular pool of glucose transporters and enhancement of glucose-transport activity. The mechanism(s) responsible for this supernormal glucose-transport activity is unknown but may be related to transient appearance of a factor coregulating cellular glucose transport and/ or modulation of the intrinsic activity of the glucose transporter.
- Received April 15, 1986.
- Revision received February 5, 1987.
- Accepted February 5, 1987.
- Copyright © 1987 by the American Diabetes Association