Effects of cytochalasin B, colchicine and vincristine on the metabolism of isolated fat-cells

Abstract

1. Colchicine and vincristine only slightly inhibit the metabolism of glucose to CO(2) and lipids by isolated fat-cells. 2. Prolonged incubation with these agents causes no further inhibition. 3. Cytochalasin B, however, inhibits glucose metabolism to both CO(2) and lipids in fat-cells. 4. However, at a concentration that causes a strong inhibition of glucose metabolism cytochalasin B is without effect on the metabolism of pyruvate, lactate or arginine to these end products. The uptake of labelled alpha-aminoisobutyrate is likewise not modified. Similarly it does not affect release of glycerol or free fatty acid, or the actions of adrenaline, insulin or caffeine on these parameters. At 10mug/ml it slightly lowers ATP concentrations, an effect that does not occur at 2mug/ml. 5. The transport of fructose into adipocytes by a specific fructose-transport system is also not affected by the agent, but the uptake of 2-deoxyglucose is strongly inhibited. It is concluded that cytochalasin B may specifically inhibit the glucose-transport system of isolated fat-cells. 6. Cytochalasin A has a much weaker action than cytochalasin B on glucose metabolism.

Role for the microtubule cytoskeleton in GLUT4 vesicle trafficking and in the regulation of insulin-stimulated glucose uptake

“…In contrast, however, microtubule depolymerization blocks insulin-stimulated glucose uptake and GFP-GLUT4 translocation to the plasma membrane by approximately 40 % ( Figure 7). These data are consistent with observations in the early 1970s which noted that colchicine partially blocked insulin-stimulated glucose oxidation and its conversion into lipids, although its effect on glucose uptake was not determined [26,27].…”

Effect of Cytochalasin B and D on Groups of Insulin Receptors and on Insulin Action in Rat Adipocytes

“…The effect of cvtochalasin B was tested on various metabolic pathways th<at are insulin sensitive. Cvtochalasin B had Ino effect on basal or epinephrine-(0.125 /ug/mnl) stimulated lipolvsis of the adipocvte (data not showiv) as reported previously bv Loten and jeainrenaud (11). Insulin (50 ,uU/ml) inhibited epinephrine-stiimiulatedl lipolysis to the same extent in the presence or absenice of cytochalasin B.…”

“…1 shows that exposure of adipocytes to a range of cvtochalasin B conieentrationis (0. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] ftM\I) for 15 min, followed by 1251-insulin (50 ,uU/ml) resulted in ac smiiall but progressive inierease in the aimounit of insulin bound with inereasinig cytochalasin Table II show that cytochalasin B inhibited basal glucose transport in a progressive fashion reaching maximal at 5 uM. Addition of cytochalasin B before the addition of 50 ,uU insulin/ ml resulted in an identical pattern of inhibition of insulin-stimulated glucose oxidation.…”

“…Cytochalasin B is known to disrupt clusters of aggregated receptors (7) and intramembranous particles (8), possibly through its actions on microfilaments and actin (9). This agent has been used to inhibit basal and insulin-stimulated glucose transport (10), but has been shown not to affect numerous other insulin-sensitive processes (11), including both membrane-localized and intracellular responses. The unaffected membrane processes include aaminoisobutyrate transport and a specific fructose transport system, whereas the unaffected intracellular insulin-sensitive action was the antilipolytic effect of the hormone.…”

Studies on the Mechanism of Mucin Secretion by Cells of the Porcine Tracheal Epithelium

“…6). COL also has been shown to decrease the uptake and oxidation of 2-deoxy-~-glucose (19) and to inhibit glucose metabolism (20,21) and nucleoside transport (22). The data strongly suggest that these agents affected the intracellular transport and release of mucin synthesized in these cells. "…”