Metabolic and ultrastructural changes induced in adipose tissue by insulin.

The addition in vitro of insulin to rat adipose tissue (epididymal) produces marked metabolic changes which may be followed by measurement of the net gas exchange of the tissue. Using this method to monitor the metabolic action of insulin, concomitant observations with the electron microscope on the tissue have been made. These reveal that pronounced morphological changes are induced by insulin. The plasma membranes of the adipose cells become invaginated at many sites to form minute finger-like indentations. Numerous tiny, membrane-bounded vesicles are also present and arranged in relationship to the plasma membrane in such a way as to suggest that their formation occurred when a recessed fold was pinched off. Deeper in the cytoplasm, especially in specimens that had been incubated a longer time, numerous large, smooth, membrane-limited vesicles are seen. Finally, in these incubated specimens the cytoplasmic matrix has lost much of its granular nature, small lipid droplets are frequently found in the cytoplasm and suggestive changes have occurred in mitochondria. In control specimens, incubated without insulin for identical periods of time, indentations and vesicles in the plasma membrane are sparse at best and no vesicles or membrane-bound spaces appear deeper in the cytoplasm. The metabolic and morphologic changes induced by insulin seem to be interdependent events. Both changes appear to be initiated rapidly and concomitantly in the tissue. Both processes are initiated by insulin at concentrations considered to be physiological, 0.004 microg. (100 microunits) per ml. Insulin treated with alkali fails to initiate either process. It is concluded that insulin initiates pinocytosis in rat adipose tissue and the possible significance of this process in the mode of action of insulin is discussed.