1. The activities of fructose 1,6-diphosphatase were measured in extracts of muscles of various physiological function, and compared with the activities of other enzymes including phosphofructokinase, phosphoenolpyruvate carboxykinase and the lactate-dehydrogenase isoenzymes. 2. The activity of phosphofructokinase greatly exceeded that of fructose diphosphatase in all muscles tested, and it is concluded that fructose diphosphatase could not play any significant role in the regulation of fructose 6-phosphate phosphorylation in muscle. 3. Fructosediphosphatase activity was highest in white muscle and low in red muscle. No activity was detected in heart or a deep-red skeletal muscle, rabbit semitendinosus. 4. The lactate-dehydrogenase isoenzyme ratio (activities at high and low substrate concentration) was measured in various muscles because a low ratio is characteristic of muscles that are more dependent on glycolysis for their energy production. As the ratio decreased the activity of fructose diphosphatase increased, which suggests that highest fructose-diphosphatase activity is found in muscles that depend most on glycolysis. 5. There was a good correlation between the activities of fructose diphosphatase and phosphoenolpyruvate carboxykinase in white muscle, where the activities of these enzymes were similar to those of liver and kidney cortex. However, the activities ofpyruvate carboxylase and glucose 6-phosphatase were very low in white muscle, thereby excluding the possibility of gluconeogenesis from pyruvate and lactate. 6. It is suggested that the presence of fructose diphosphatase and phosphoenolpyruvate carboxykinase in white muscle may be related to operation of the o-glycerophosphate-dihydroxyacetone phosphate and malate-oxaloacetate cycles in this tissue.The enzyme PFK$ (ATP-D-fructose 6-phosphate 1-phosphotransferase, EC 2.7.1.11) in muscle has been shown to be a regulatory enzyme for glycolysis, and, on the basis of the properties of this enzyme, a theory for metabolic control has been proposed

1. The present study extends the finding of Krebs & Woodford (1965) that muscle fructose diphosphatase is more sensitive to AMP inhibition than liver fructose diphosphatase. 2. Hen breast fructose diphosphatase has a K(i) for AMP of 0.1mum; the plot of percentage inhibition is non-sigmoid and the reciprocal plot of activity against AMP concentration is sometimes linear. 3. Percentage inhibition plots for other muscle fructose diphosphatases are sigmoid curves which exhibit different threshold responses to the AMP concentration. 4. The intracellular content of AMP in all muscles tested exceeds the inhibition concentration range of AMP. 5. The sensitivity of muscle fructose diphosphatase to AMP inhibition is decreased by the presence of Mg(2+) or Mn(2+) ions; in the presence of Mn(2+) the inhibition curve for hen breast fructose diphosphatase becomes sigmoid. 6. From the formation constants for the Mg(2+) and Mn(2+) chelates, the effect of these ions in chelation of AMP can be calculated. Although chelation of AMP can explain the Mg(2+) effect, it cannot explain the marked relief of AMP inhibition by Mn(2+). 7. It is suggested that Mn(2+) has a specific effect on this enzyme which reduces the sensitivity to AMP inhibition.

SUMMARY 1. An augmented insulin tolerance test and its normal response is described; after a standard preparation, 11·1 u. of soluble insulin/m.2 of body surface is injected intravenously, and the level of blood sugar followed for 2 hr. 2. The degree of insulin resistance, in such states as acromegaly, can be indexed by the sum of the blood sugar values, as mg./100 ml., at 60, 90 and 120 min. after insulin. In normal subjects the mean 'insulin resistance index' was 92 (range 62–142). The test is valid only if the fasting blood sugar is normal. 3. Results are reported in: (a) twelve 'untreated' acromegalics in all of whom the test showed an abnormal insulin resistance index (mean 173 and range 144–228); (b) fourteen treated acromegalics (after gold-198 or yttrium-90 implants), in eight of whom the insulin resistance index was normal, although only five were judged to be in full clinical remission; (c) twelve subjects with gross but 'simple' obesity in whom the test results were nearly as abnormal as those of the 'untreated' acromegalics (mean insulin resistance index 159 and range 119–221). 4. The test can be used to assess the 'activity' of acromegaly and its response to treatment, provided the subject is not also grossly obese.

539hypertensive action of ketanserin is thus characterised by a favourable haemodynamic profile. The observation that ketanserin lowered not only systemic arterial pressure but also cardiac filling pressures suggests that this balanced vasodilatation may be of particular interest for the treatment of congestive heart failure. Indeed, a favourable response to ketanserin in this condition has been reported recently."' 5-HT not only acts as a direct vasoconstrictor, but it also amplifies the vasoconstrictor responses to agents such as noradrenaline and angiotensin II.2 5-HT is released by aggregating platelets in atherosclerotic arteries, which are abnormally responsive to this amine.'2 Ketanserin antagonises not only the direct vasoconstrictor effect of 5-HT but also its amplifying effects on other vasoactive substances.5 These mechanisms may all be implicated in the haemodynamic effects of 5-HT2 receptor blockade by ketanserin. This compound is thus a new therapeutic tool for investigating the role of 5-HT in the pathogenesis of various forms of hypertension. Experience so far warrants further assessment of its place in the management of hypertension.We thank Dr J Symocns of Janssen Pharmaceutica for generous supplies of ketanserin. Sodium-potassium cotransport activity is thought to be defective in essential hypertension and could be a useful genetic marker for susceptibility to essential hypertension. In this study cotransport activity in subjects with hypertension was compared with that in normotensive controls. The effects of ethnic differences, environment, and antihypertensive drugs were also studied. Mean cotransport activity was lower in hypertensive subjects than in controls of the same ethnic groups. There was, however, a large overlap between controls and hypertensive subjects. No ethnic or environmental influences were found. The large overlap found suggests that sodium-potassium cotransport activity is not a useful genetic marker in essential hypertension. References

No abstract