Actions of peroxovanadate or tungstate on glucose transport by isolated rat adipocytes

The effects of peroxovanadate or tungstate on 3-O-methylglucose uptake were characterized using isolated rat adipocytes to elucidate the mechanism(s) of their actions. The stimulatory effect of peroxovanadate was observed from 1 μmol/L and reached the maximum at about 100 μmol/L. The concentration showing the half-maximal effect was approximately 16 μmol/L. The maximal response of peroxovanadate was 1.19 times higher than that of insulin significantly (P < 0.01). On the other hand, the stimulatory effect of tungstate was seen only at the higher concentrations of 10–30 mmol/L Judging from the experiments using different tungsten compounds, tungstic acid (WO₄^2-) appeared responsible for the effect. The effects of 20 mmol/L tungstate and 20 nmol/L insulin were not additive. The stimulatory effects of 1 mmol/L peroxovanadate, 20 mmol/L tungstate or 20 nmol/L insulin were not seen in the adipocytes deprived of ATP by exposure to 2 mmol/L KCN. The adipocytes which had been stimulated with insulin and further exposed to 2 mmol/L KCN were used to test whether or not peroxovanadate works directly on the function of glucose transporters. In such cells on which GLUT4-rich transporters were rendered immobile, the effect of peroxovanadate was not observed. These results indicate that the effects of peroxovanadate or tungstate are ATP or energy dependent and may be exerted through the mechanism analogous to that of insulin action, and suggest that peroxovanadate does not directly activate the function of GLUT4.     

A case of Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction

A case of a 6 year old boy with Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction is reported. Magnetic resonance imaging revealed abnormal findings of the pituitary gland and stalk. Good catch-up growth was obtained by treatment with growth hormone. These findings suggest that hypothalamic-pituitary dysfunction might be involved in Kabuki make-up syndrome.     

Inhibitory effects of diazoxide or polymyxin B on glucose transport by isolated rat erythrocytes or adipocytes

The inhibitory effects of diazoxide or polymyxin B on 3-O-methylglucose uptake were studied in isolated rat erythrocytes or adipocytes to elucidate the mechanisms of the actions of these agents. One to three mmol/L diazoxide significantly inhibited 3-O-methylglucose uptake into erythrocytes by 11–33% without altering the equilibrium space, while 0.3 mmol/L diazoxide did not. The inhibitory effect was exerted in a dose-dependent manner in this concentration range. To test whether polymyxin B affects the process of insulin action or the glucose transport activity recruited by insulin, adipocytes prestimulated with insulin and exposed to 2 mmol/L potassium cyanide (KCN) were employed since the cells, on which glucose transporters recruited by insulin were located quiescently, were useful to estimate the effect of an agent on glucose transport activity per se. Polymyxin B (100 μg/mL) inhibited the insulin-stimulated uptake activity in this transport system by 22.5% while it inhibited the insulin-stimulated uptake activity in intact adipocytes which were not exposed to KCN by 32.2%. These results suggest that diazoxide inhibits the function of the erythrocyte glucose transporter, GLUT1*** (classified by Bell et al.), and indicate that the inhibition of the glucose transport activity recruited by insulin is the major effect of polymyxin B (100 μg/mL) and the inhibition of the process of insulin action is rather small.     

An extrapancreatic action of diazoxide to inhibit glucose transport activity on adipocytes

The effect of diazoxide on 3-O-methylglucose (3-O-MG) transport was studied in isolated rat adipocytes to elucidate its extrapancreatic action. Diazoxide (0.3-3 mmol/L) significantly inhibited 3-O-MG uptake into adipocytes in a basal state or an insulin-stimulated state. The inhibitory effect was mainly due to the inhibition of insulin responsiveness for 3-O-MG uptake. The insulin responsiveness is determined by the capacity in the process of insulin action and in the final glucose transport activity, and diazoxide mainly inhibited the 3-O-MG transport activity itself. Based on these findings, this extrapancreatic action of diazoxide is considered to contribute partially to raising the blood glucose level in children receiving the drug. Diazoxide, as a glucose transport inhibitor, may be a useful tool for studying the issues related to glucose transport or insulin action.