Richard S. Haber

GLUT1 glucose transporter expression in colorectal carcinoma

Malignant cells exhibit increased glycolytic metabolism, and in many cases increased glucose transporter gene expression. The authors hypothesized that GLUT1 glucose transporter expression is increased in colorectal carcinoma, and that the degree of expression might have prognostic significance.

Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with 99mtechnetium sestamibi scintigraphy

objective To determine the utility of ultrasonography for the preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism, and to compare this method with 99mtechnetium sestamibi scintigraphy.

Glucocorticoid-Induced Insulin Resistance: Dexamethasone Inhibits the Activation of Glucose Transport in Rat Skeletal Muscle by Both Insulin- and Non-Insulin-Related Stimuli

To test the hypothesis that glucocorticoids inhibit muscle glucose transport apart from changes in early insulin-signaling events, we determined the effect of glucocorticoid treatment on the activation of glucose transport by both insulin and non-insulin-related stimuli (insulin-like growth factor [IGF] I and hypoxia) in rat skeletal muscle. Male Sprague-Dawley rats were treated with dexamethasone (Dex) (0.8 mg/kg for 2 days) and compared with pair-fed controls. 2-[3H]deoxyglucose (2-[3H]DG) uptake in isolated soleus muscles was measured under conditions in which uptake reflects glucose transport activity. In control muscles, 2-[3H]DG uptake was stimulated 10-fold by insulin (10 nmol/l) or IGF-I (50 nmol/l) and sixfold by hypoxia. Dex treatment decreased 2-[3H]DG uptake at all concentrations of insulin tested, reducing maximal insulin-stimulated 2-[3H]DG uptake by 41 ± 11% (mean ± SE, P < 0.05) and basal 2-[3H]DG uptake by 38 ± 6% (P < 0.01). Dex treatment also inhibited 2-[3H]DG uptake at all concentrations of IGF-I tested, reducing maximal IGF-I-stimulated 2-[3H]DG uptake by 29 ± 2% (P < 0.01), and decreased hypoxia-stimulated 2-[3H]DG uptake by 61% (P < 0.01). Dex treatment increased soleus GLUT4 protein content by 11%. Thus, Dex treatment reduces basal glucose transport and decreases the maximal response of skeletal muscle glucose transport to insulin, the related hormone IGF-I, and the non-insulin-related stimulus hypoxia. These findings support the hypothesis that, in addition to altering early insulin-signaling events, glucocorticoids may also act by inhibiting the glucose transport system, per se, perhaps by affecting GLUT4 subcellular trafficking.

Targeted parathyroidectomy in the era of intraoperative parathormone monitoring.

nA combination of preoperativenlocalization and intraoperative parathormone (PTH) monitoring permitsntargeted parathyroidectomy. Multiple approaches have been developed,nranging from unilateral neck exploration (UE) to radio-guidednparathyroidectomy (RP) to endoscopic parathyroidectomy (EP). Thenpurpose of this study was to evaluate the efficacy of these approachesnin the management of primary hyperparathyroidism. From June 1998 tonNovember 2000 a total of 110 targeted parathyroid operations werenperformed at a university medical center. All patients underwentntechnetium-99m-sestamibi scanning, ultrasonography, or both prior tonsurgery. Intraoperative PTH monitoring was utilized in all cases.nThirty-seven patients underwent UE, 59 underwent RP, and 14 underwentnEP. Follow-up ranged from 1 to 24 months. All patients were curednfollowing parathyroidectomy as predicted by a more than 50% reductionnof the intraoperative PTH level following removal of all hypersecretingnglands. Altogether, 103 patients had a solitary adenoma (95%), and 1npatient had a parathyroid carcinoma. Six patients (5%) had multiglandndisease, including four cases of hyperplasia and two patients with andouble adenoma. Eighty-three patients (75%) were discharged the day ofnsurgery. The use of preoperative localization and intraoperative PTHnmonitoring permits a targeted approach to the treatment of primarynhyperparathyroidism. Endocrine surgeons should be facile in allnminimally invasive parathyroid techniques to individualize thenoperative approach.nn

Effects of thiazolidinediones on glucocorticoid-induced insulin resistance and GLUT4 glucose transporter expression in rat skeletal muscle.

Thiazolidine-2,4-diones, a new class of oral antihyperglycemic agents, have been shown to be effective in improving insulin sensitivity in a number of animal models of insulin resistance, and recent investigation has suggested that the mechanism of action of these agents may include upregulation of the GLUT4 (insulin-regulatable) glucose transporter. We studied the efficacy of two of these agents, pioglitazone and englitazone, in preventing glucocorticoid-induced insulin resistance in rats, and examined the potential role of changes in GLUT4 expression in their action in skeletal muscle. Rats were treated with 0.1 mg/d dexamethasone for 6 to 7 days with or without either pioglitazone (10 mg/kg/d) or englitazone (50 mg/kg/d). Both thiazolidinediones decreased the elevated fasting serum glucose and insulin levels in dexamethasone-treated animals. Dexamethasone treatment alone decreased insulin-stimulated 2-deoxyglucose uptake into isolated soleus muscles to 35% of control values. The addition of pioglitazone or englitazone increased insulin-stimulated 2-deoxyglucose uptake by 74% and 57%, respectively. Whereas dexamethasone treatment alone increased GLUT4 protein content in rat soleus muscle by 25%, additional treatment with pioglitazone or englitazone did not further significantly alter GLUT4 levels. We conclude that thiazolidinediones enhance insulin responsiveness in skeletal muscle during glucocorticoid treatment, but their mode of action in this setting is not via upregulation of GLUT4 expression.

Differential regulation of glucose transporter isoforms by thyroid hormone in rat heart.

Since thyroid hormone stimulates cardiac metabolism, for which glucose is an important fuel, we examined the effects of thyroid hormone on glucose transporter gene expression in rat heart. Treatment of hypothyroid animals with T3 for up to 6 days caused a 2-fold increase in GLUT4 mRNA at 1 day, and a 4-fold increase at 6 days (per unit DNA). GLUT4 protein, however, was not increased. In contrast, GLUT1 mRNA was transiently decreased by T3 treatment at 1 and 3 days, but returned to normal by 6 days. Concomitantly, GLUT1 protein decreased to 18% of the control value at 6 days. In chronically hypothyroid or hyperthyroid rats, GLUT4 mRNA varied directly with thyroid status, but GLUT4 protein was invariant, consistent with the acute effects of T3 treatment. Moreover, hypothyroidism increased GLUT1 mRNA and protein expression. We conclude that, in contrast to previous observations in skeletal muscle, GLUT4 protein content in rat heart is not altered by thyroid hormone. Cardiac GLUT1 expression is increased in hypothyroidism, and suppressed by thyroid hormone, at both the protein and mRNA levels. The observed discrepancy between GLUT4 mRNA and protein levels suggests that post-transcriptional regulatory events play a major role in GLUT4 expression in rat heart.

Ultrasound-Guided Fine Needle Aspiration Biopsy of Thyroid Nodules

Cytologic examination of fine needle aspiration (FNA) specimens from thyroid nodules is the key test for the evaluation of thyroid nodules, and the results are critical in the selection of patients with nodules for thyroid surgery. Although needle placement for FNA is traditionally and most commonly guided by nodule palpation alone, the widespread availability of thyroid ultrasonography has made possible a technical refinement of this technique, needle placement under ultrasonographic guidance. Ultrasound-guided FNA is often valuable, and sometimes essential, in obtaining accurate diagnostic material. This chapter reviews the role of ultrasound-guided fine needle aspiration (UG FNA) in the diagnosis of thyroid nodules.