Effect of dexamethasone on insulin binding, glucose transport, and glucose oxidation of isolated rat adipocytes.

Abstract

A B S T R A C T We have studied the in vitro effects of dexamethasone on isolated rat adipocytes at concentrations of dexamethasone therapeutically achieved in man. Glucose oxidation, glucose transport, and insulin binding were assessed. In dexamethasone-treated cells, glucose oxidation was decreased by 30-40% both in the absence of insulin (basal state) and at low insulin levels (less than 25 AsU/ml). At maximally effective insulin levels (over 100 F'U/ml) no differences existed between control and treated cells. If glucose transport were the ratelimiting step for glucose oxidation in the basal state and at low (submaximal) insulin levels, but not at maximally effective insulin concentrations, then these data could be explained by postulating that dexamethasone has a direct affect on glucose transport and does not affect intracellular oxidative pathways. We tested this hypothesis by directly assessing glucose transport in dexamethasone-treated cells. Glucose transport was assessed by measuring the uptake of [14C]2-deoxy glucose. These studies demonstrated a 30-40% decrease in 2-deoxy glucose uptake by treated cells both in the basal state and at all insulin concentrations. Thus, a direct glucocorticoid effect on the glucose transport system seems to account for the decreased ability of dexamethasone-treated cells to oxidize glucose. Since dexamethasone treatment leads to decreased insulin binding to adipocytes in vivo, we examined the possibility that the in vitro decreases in insulin-mediated glucose transport could be due to decreased insulin receptors. Insulin binding to control and treated adipocytes was measured, and no differences were found. Therefore, in contrast to previously reported in vivo studies, adipocytes treated in vitro with Dr. Olefsky is a Restarch Associate with the Veterans Administration (MRIS #6488).

Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

“…Insulin action on target tissues might be altered by a decreased receptor number and/or affinity, or by a post-receptor defect [13,14]. Changes in the levels of counterregulatory hormones could also be involved, e. g. glucagon stimulates insulin-inhibited hepatic glucose production [14].…”

Naphthalenemethyl ester derivative of dihydroxyhydrocinnamic acid, a component of cinnamon, increases glucose disposal by enhancing translocation of glucose transporter 4

“…Epididymal adipose tissue was removed from 5-week-old male Sprague-Dawley rats and digested with collagenase type II (1 mg/ml; Sigma Chemical, St. Louis, MO, USA) in 1 ml Krebs-Ringer HEPES (KRH) buffer (131 mmol/l NaCl, 4.7 mmol/l KCl, 2.5 mmol/l CaCl 2 , 1.25 mmol/l MgCl 2 , 2.5 mmol/l NaH 2 PO 4 , 10 mmol/l HEPES, pH 7.4) supplemented with 1% BSA and 2 mmol/l pyruvate for 1 h at 37°C [16]. After digestion, adipocytes were prepared as described previously [17].…”

Dexamethasone-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than insulin signal transduction.

“…Diabetes 49:1700-1708, 2000 R esearch has shown that glucocorticoids are hormones that induce insulin resistance and that their clinical use often exacerbates diabetes (1)(2)(3). This glucocorticoid-induced insulin resistance has been demonstrated not only in clinical cases but also in animal experiments (4,5) and in vitro experiments using isolated or cultured cells (6)(7)(8). For example, in skeletal muscle of glucocorticoid-treated rats, increases in glucose uptake induced by insulin, IGF-I, or hypoxia were found to be decreased (9,10).…”