European Association for the study of Diabetes First Annual Meeting, Montecatini Terme, 20. IV.-22.IV. 1965

Abstract

The fact that one of the major actions of insulin on muscle is to stimulate passage of glucose across the membrane makes it unlikely ~hat effects of the hormone are to be seen in cell-free systems, and indeed few observations of this sort have been reported. Likewise, if the stimulation by insulin of incorporation of amino acids into protein arises from an action of the hormone to regulate the intracellular distribution and availability of ATP we should again expect the capacity of a tissue to respond to insulin to be lost on homogenisation. If, on the other hand, the effect of insulin on amino acid incorporation were to result from a direct interaction of the hormone with the protein synthesizing system, such an effect might still be seen in a cell-flee system. It was thus thought of interest to seek to establish whether insulin could influence amino acid incorporation in homogenates or under conditions in which the membrane characteristics of muscle were varied by changes in the ion content of the supporting buffer. In general the effect of insulin is nbt seen in these broken cell preparations, from Which observations conclusions as indicated above can be drawn. However, a number of behavioural characteristics of the incorporating system lead to the belief that the optimal conditions for protein synthesis in cell-free preparations have yet to be discovered and an effect of insulin in these circumstances may be dependent on satisfying a number of conditions as yet inadequately determined. It is hoped to discuss observations bearing on these problems. Some relationships between cation transport, carbohydrate metabolism and insulin action in muscle.T. CLAUSEI~. Inst. of Physiology, Univ. of Aarhus.Isolated rat and mouse hemidiaphragms were incubated in Krebs-Ringer bicarbonate buffer. The active transport of Na + and I~+ across cell membranes is known to be decreased in potassium-free media. Lowering of the K+-concentration from 6 to 0 mM/L was shown to cause up to 200% stimulation of 14C-glycogen synthesis in the diaphragm. This insulin-like effect was not paralleled by an increased glucose uptake. However, the increased glycogen synthesis was followed by a decreased lactate production. Ouabain (g-strophantine), which is a potent inhibitor of active cation transport was shown at normal K+-concentration to produce essentially the same effects when added to the incubation medium. Changes in the sodium concentration of the incubation medium had the following effects : the glucose uptake and lactic acid production were stimulated at concentrations of sodium higher than normal, and inhibited at concentrations lower than normal; the stimulation of glucose uptake by insulin (0.1 i. u./ml) was most pronounced at 143 mmol of sodium, being diminished both at the higher and the lower concentration of sodium; the stimulatory effect of insulin upon glycogen synthesis and lactate production was correspondingly diminished at high and low concentrations of sodium. It is suggested that the cation transport plays a central role in...