We have studied the relationship between insulin activation of insulin-receptor kinase and insulin stimulation of glucose uptake in isolated rat adipocytes. Glucose uptake was half-maximally or maximally stimulated, respectively, when only 4 % or 14 % of the maximal kinase activity had been reached. To investigate this relationship also under conditions where the insulin effect on activation of receptor kinase was decreased, the adipocytes were expos'ed to 10 ,uM-isoprenaline alone or with 5 jug of adenosine deaminase/ml. An approx. 30 % (isoprenaline) or approx. 50 % (isoprenaline + adenosine deaminase) decrease in the insulin effect on receptor kinase activity was found at insulin concentrations between 0.4 and 20 ng/ml, and this could not be explained by decreased insulin binding. The decreased insulin-effect on kinase activity was closely correlated with a loss of insulin-sensitivity of glucose uptake. Moreover, our data indicate that the relation between receptor kinase activity and glucose uptake (expressed as percentage of maximal uptake) remained unchanged. The following conclusions were drawn. (1) If activation of receptor kinase stimulates glucose uptake, only 14 % of the maximal kinase activity is sufficient for maximal stimulation. (2) Isoprenaline decreases the coupling efficiency between insulin binding and receptor-kinase activation, this being accompanied by a corresponding decrease in sensitivity of glucose uptake. (3) Our data indicate that the signalling for glucose uptake is closely related to receptor-kinase activity, even when the coupling efficiency between insulin binding and kinase activation is altered. They thus support the hypothesis that receptor-kinase activity reflects the signal which originates from the receptor and which is transduced to the glucosetransport system. INTRODUCTIONThe insulin receptor is a transmembrane glycoprotein composed of two a-subunits of 135 kDa and two f-subunits of 95 kDa [1,2]. Insulin binding to the a-subunits causes rapid phosphorylation of tyrosine residues on the fl-subunits [1,3]. The phosphorylation of tyrosine-containing sites on the receptor in turn activates the insulin-receptor kinase toward tyrosine residues of other protein substrates [4][5][6]. Several lines of evidence indicate that autophosphorylation and activation of the insulin receptor as a tyrosine kinase is an important early step necessary for the transduction of many, if not all, of the biological effects of insulin [1,7,8]. A decreased ability of insulin receptors to autophosphorylate or to activate their kinase in response to insulin could therefore cause or contribute to insulin resistance. In fact, a decreased kinase activity of insulin receptors has been found in a variety of situations where the effects of insulin on biological actions are decreased [9][10][11][12][13][14], including type-II diabetes [15][16][17]. For technical reasons it has, however, so far been difficult to relate directly alterations in the coupling between insulin binding and insulin-induced activation o...

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I n the German Democratic Republic, as in other highly developed countries, the number of people weighing more than is normal has steadily increased since the end of World War 11. A recent survey showed that 32.6% of the entire population are overweight. T h e number of obese women is very much larger than that of obese men, the percentages being 42-2 and I 9.2% respectively. Especially threatening is the increase in the incidence of obesity with advancing age. Epidemiological investigations show that the number of overweight persons is particularly great among the middle-aged and aged. This is particularly true of women as more than 50% of women in their fifties must be considered as having adiposity.No wonder that the question as to the causes of excessive increases of weight has been raised time and again. Adiposity-at least in the light of pathogenetic principlesmust be considered to be the result of an overbalance. Accordingly, it is the result of either hyperphagia or hypomotility. However, it has not yet been possible to answer unambiguously the question of the relative importance and interrelationships of the two phenomena. But the statement that obesity must be considered the result of an overbalance does not provide an answer to the question of the causes of the disorder, that is, its aetiology. It is true that we know how obesity develops, but what we lack is knowledge of why people tend to take insufficient exercise or why they eat too much or have diets based on improper principles. A discussion of the harmful factors involved will not, however, be the subject of this paper.T h e assumption that an increase of weight may be triggered by improper nutrition, which is entirely correct from a pathogenetic point of view, has always been a matter of controversy. For example, the counter-arguments were that not all of the 'fatties' eat too much, that not all of the gluttons are fat, that not all persons weighing more than normal show a loss of weight when put on a restricted diet, and that some people would even grow stouter when put on a limited diet. Therefore, it is necessary to analyze exactly the eating habits of obese persons with a view to clarifying the actual situation. It was by extensive and intensive studies made within the framework of a large-scale research project that we endeavoured to make a major cuntribution to this all-important question."

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