Modulation by Calcium of the Insulin Action and of the Insulin-Like Effect of Ocytocin on Isolated Rat Lipocytes

Activation of glucose oxidation in isolated rat fat cells by insulin involves both calcium-dependent and calcium-independent mechanisms. When the exocellular calcium concentration is below 50 μM, only 50% of the maximum response of these cells to insulin is measured. The maximal stimulation is attained for roughly millimolar concentration of the divalent cation. Similarly, the insulin-like effect of ocytocin appears in the same range of Ca2+ concentrations for which the maximum insulin effect is measured. Cobalt ions appear to suppress the additional activation by Ca2++ insulin and to affect totally the stimulation by ocytocin. Neither the Ca2+ ionophore A23187 nor verapamil affect these phenomenon suggesting that these activations are not directly connected with transmembrane Ca2+ transport. These observations might reflect the existence of two distinct mechanisms of insulin action. They also show that a similarity exists between the mode of action of the neurohypophyseal nonapeptide and the calcium-dependent mechanism of insulin action on these cells. Based on the observation presented here and on the reported evidence for a specific, insulin-dependent, Ca2+ binding on lipocytes membranes [Proc. Natl Acad. Sci. U.S.A. (1976) 73, 1542–1546], it is postulated that this divalent cation may act as a modulator of the hormonal action through structural effects on the elements of the lipocytes membrane transducing systems.