Metabolism of Isolated Fat Cells
II. THE SIMILAR EFFECTS OF PHOSPHOLIPASE C (CLOSTRIDIUM PERFRINGENS
TOXIN) AND OF INSULIN ON GLUCOSE AND AMINO ACID METABOLISM
Martin Rodbell 1
From the
1 From the Section on Endocrinology, Laboratory of Nutrition and Endocrinology, National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland 20014
Phospholipase C (
toxin of Clostridium perfringens) has been found to cause, at relative high concentrations, the lysis of fat cells isolated from rat epididymal adipose tissue. Lysis of the fat cells resulted in the loss of insulin response in proportion to the amount of cells broken. It is suggested that the effects of insulin on glucose metabolism by the fat cell are dependent on the presence of an intact cell membrane.
The level of flexokinase activity in the fat cell was not affected by insulin or phospholipase C; sufficient hexokinase was present to account for all the glucose phosphorylated by fat cells in response to insulin.
Evidence is presented that glucose is transported in the fat cell by a carrier-mediated, stereospecific process. Insulin and treatment of fat cells with phospholipase C under conditions that did not cause lysis, stimulated the transport of glucose. Anabolic processes, such as fatty acid synthesis from glucose and amino acid incorporation into protein, were also stimulated by insulin and phospholipase C. The action of phospholipase C on glucose transport and amino acid utilization was a function of enzyme concentration, suggesting that the amount of cellular phospholipid hydrolyzed by the enzyme determined the amount of solute entering the cell. Phospholipids appear, therefore, to be linked to transport processes.
The common effects of insulin and phospholipase C on the fat cell suggests that the same parameter in the cell is affected by these substances. It is hypothesized that insulin and phospholipase C act on the plasma membrane to alter the configuration of its lipoproteins from a laminated to a micellar or globular form. The latter configuration of the membrane lipoproteins might have interstices that permit the carrier-mediated passage of solutes into the cell.
Submitted on July 15, 1965