Effect of Cytochalasin B and D on Groups of Insulin Receptors and on Insulin Action in Rat Adipocytes
Open Access
- 1 April 1979
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 63 (4), 571-579
- https://doi.org/10.1172/jci109338
Abstract
The possible physiological importance of the groups of insulin receptors on rat adipocytes and the relationship of these groups to insulin action were investigated. The effect of cytochalasin B and D on biological actions of insulin was measured and compared with the effect of these agents on the ultrastructural distribution of groups of insulin receptors. Cytochalasin B had no effect on epinephrine-stimulated lipolysis, insulin inhibition of epinephrine-stimulated lipolysis, or insulin stimulation of protein synthesis. Cytochalasin B, over a concentration range of 50 nM to 5 μM, progressively inhibited the basal glucose transport system, as measured by glucose oxidation, 2-deoxyglucose transport, and 3-O-methylglucose transport. Insulin was capable of fully stimulating remaining basal transport at submaximal concentrations of cytochalasin B. Insulin pretreatment of adipocytes partially protected the glucose transport system from inhibition by cytochalasin B. Cytochalasin B markedly altered the distribution pattern of insulin receptors, which caused an increase in the number of single receptor molecules by decreasing the number of larger groups. A significant correlation (r = 0.964; P < 0.001) was found between the percent increase in single receptors and the percent decrease in glucose transport. Ferritin-insulin pretreatment of adipocytes prevented disruption of the groups of insulin receptors by cytochalasin B. Cytochalasin D had no effect on the biological actions of insulin or on the groups of insulin receptors. These data suggest that the ability of insulin to affect adipocyte metabolism is independent of the hormone occupying adjacent, grouped receptor sites. The marked contrast in effects of cytochalasin B and D on groups of insulin receptors and glucose transport suggests that the microfilament system is not involved in insulin action or in holding the groups of insulin receptors together, as both agents are known disrupters of microfilaments and inhibitors of actin gelation. The correlation between the effects of cytochalasin B on insulin receptor distribution and glucose transport leads to the speculation that the glycoprotein molecules containing the insulin receptor are functionally linked with the glucose transport system.This publication has 40 references indexed in Scilit:
- Antibodies to Purified Insulin Receptor Have Insulin-Like ActivityScience, 1978
- Antibodies against intrinsic adipocyte plasma membrane proteins activate D-glucose transport independent of interaction with insulin binding sites.Journal of Biological Chemistry, 1978
- Anti-insulin receptor antibodies inhibit insulin binding and stimulate glucose metabolism in skeletal muscleDiabetologia, 1978
- Actin-related gelation of Ehrlich tumour cell extracts is reversibly inhibited by low concentrations of Ca2+Nature, 1978
- Peptide hormone receptors.Annual Review of Physiology, 1977
- The natural occurrence of insulin receptors in groups on adipocyte plasma membranes as demonstrated with monomeric ferritin‐insulinJournal of Supramolecular Structure, 1977
- Cell surface receptors for insulin and human growth hormone. Effect of microtubule and microfilament modifiers.Journal of Biological Chemistry, 1976
- Effect of Ischemia on Known Substrates and Cofactors of the Glycolytic Pathway in BrainJournal of Biological Chemistry, 1964
- METABOLISM OF ISOLATED FAT CELLS .I. EFFECTS OF HORMONES ON GLUCOSE METABOLISM + LIPOLYSIS1964
- A convenient, rapid and sensitive method for measuring the incorporation of radioactive amino acids into proteinBiochemical and Biophysical Research Communications, 1960