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NOBEL PRIZE IN MEDICINE
913
blood, and from this observation they conclude thatWINSTON EVANS, LITTLER, and PEMBERTON 44 have
glucagon does not interfere with the peripheral uptake llately described 4 uncontrolled young diabetics of glucose. The same conclusion may be drawn from with large livers in which an excess of glycogen was In 3 of them, after an infusion of glucagon : the experiments of HUBBLE,39 who found that the fall found. of the blood-sugar curve in 17 diabetics after an the blood-sugar rose only by 85, 20, and 35 mg. per injection of glucagon closely paralleled the fall seen in 100 ml.-a result attributed- by the investigators to the glucose-tolerance test of these same diabetics. Inimpaired glycogenolysis. One may assume that the 3 thyrotoxic diabetics, on the other hand, the blood-height of the fasting blood-sugar must have some sugar fall was faster after glucagon hyperglycsemia influence on the capacity of the liver to mobilise than after alimentary hyperglycoemia. VOLK et aL40 glycogen, and in these cases the fasting blood-sugars report a diminished insulin sensitivity in hyperthyroid were 425, 420, and 450 mg. per 100 ml. It would dogs, which they attribute to the rapid breakdown of have been valuable to have repeated the glucagon hepatic glycogen in the hyperthyroid state-a break- test after insulin, as in the child whose case is down faster than the uptake (also rapid) of glucose quoted above. Moreover, it has already been demonThe distinction between strated that in such uncontrolled cases, with glycogenat the periphery. glucagon and which filled livers, an injection of adrenaline provokes a alimentary hyperglycsemia hyperglycaemia HUBBLE observed in thyrotoxic diabetics could thus normal glycogenolytic response.45 Adrenaline (probe explained by glucagon having emptied the liver of vided it is not used in an impotent solution 46 47) its glycogen, leaving little to be mobilised later by remains both a more powerful and a more accessible thyroxine. VAN ITALLIE et a1.38and HuBBLE 39 exam- glycogenolytic agent than glucagon. ined the effect on the blood-sugar of glucagon given with an intramuscular injection of adrenaline. The Annotations blood-sugar curves were considerably higher than when NOBEL PRIZE IN MEDICINE glucagon alone was injected-from which HUBBLE infers that glucagon does not inhibit the glycogenoTHE award of the Nobel prize in physiology and lytic effect of adrenaline on muscle, whereas VAN medicine to Prof. Hugo Theorell of the Nobel Institute, ITTALIE and his colleagues conclude that adrenaline Stockholm, represents the second occasion on which inhibits peripheral glucose uptake. This conclusion this honour has been given to a compatriot of the they support by showing that the capillary-venous founder. Professor Theorell’s fundamental contribution to the differences in the blood-sugar were almost removed by of cell was made in the the action of adrenaline. Glucagon then is not an insulin-antagonist; its site of origin is still undetermined ; and its hormonal status is uncertain. Indeed, if it is a hormone it probably acts synergistically with insulin, by making hepatic glycogen available for insulin action at the periphery.4142 ANDERSON 43 has reviewed the experimental evidence which suggests that glucagon not only potentiates the action of insulin, but also stimulates its production during the postabsorptive period. If the place of glucagon in human physiology is still unsettled, its use in pathological diagnosis requires critical examination. KIRTLEY et al.32 used glucagon in 8 diabetics, and on the shape of the consequent blood-sugar curves they divided these diabetics into two groups. 4 who were young and thin, in whom the diabetes was labile and ketotic, showed a small rise and a rapid fall; while 4 elderly, obese, and non-ketotic diabetics showed a higher rise and a slow fall. By the response to glucagon, the well-known insulin-sensitive and insulin-insensitive types could thus be differentiated. But HUBBLE, having repeated this work and compared the results with the Himsworth insulin-glucose-tolerance test, the insulintolerance test, the glucose-tolerance test, and the patient’s clinical type, does not believe that any such differentiation is possible by the injection of glucagon. Several of his elderly and obese diabetics showed only a small rise (less than 25%) over the fasting bloodwhile in one child diabetic the response of the sugar, to was increased from 18 to 53% blood-sugar glucagon a meal and the test was made. insulin before by giving
39. Hubble, D. Diabetes, 1955, 4, 197. 40. Volk, B. W., Lazarus, S. S., Lew, H. Metabolism, 1955, 4, 10. 41. Pincus, I. J., Rutman, J. Z. Arch. intern. Med. 1953, 92, 666. 42. MacCrath, W. B., Snedecor, J. G. Diabetes, 1953, 2, 443. 43. Anderson, G. Science, 1955, 122, 457.
study
early ’thirties,
respiration
when he isolated the " yellow respiratory enzyme" in crystalline form. Other contemporaries-notably Otto Warburg, another Nobel prizeman-helped to define the chemical nature of this enzyme ; but to Theorell goes the credit for showing that the enzyme could be reversibly split into two inactive portionsnamely, a prosthetic group (riboflavine phosphate) and a protein carrier. This enzyme is now known as the " old yellow enzyme " to distinguish it from other yellow respiratory ferments that have since been discovered. Of late years Professor Theorell has added notably to our knowledge of oxidase enzymes of the cytochrome type. These enzymes are also associated with cell respiration and act in conjunction with the flavine enzymes. VASOMOTOR HEADACHE AND EPILEPSY THE borderlands of epilepsy constitute a perpetual diagnostic problem. At what stage, for instance, should we term " epileptic " the patient who repeatedly has sudden brief loss of consciousness, often with pallor and perhaps occasionally a little minor twitching, and In such cases whose attacks appear quite causeless considerable reliance has been placed on electroencephalography, which occasionally gives an unequivocal But as our knowledge of the range of normal answer. has increased the number of records regarded as decisive has been reduced, and we have been left increasingly to make a clinical decision. Heyck and Hess,48 working in Prof. H. Krayenbiihl’s clinic in Ziirich, seek to extend this borderland a little. They find that of 200 patients with severe episodic vasomotor headache 20 showed evidence of epileptic dysrhythmia in their electro-encephalograms, particularly after photic stimulationand of 48 patients with classical ’
44. Evans, R. W., Littler, T. R., Pemberton, H. S. J. clin. Path. 1955, 8, 10. 45. Houet, R. Pr. méd. 1949, 12, 159. 46. Crawford, T. Quart. J. Med. 1946, 15, 285. 47. Hubble, D. Lancet, 1954, i, 235 48. Heyck, von H., Hess, R. Schweiz. Med. Wschr. 1955, 85, 573.
blood, and from this observation they conclude thatWINSTON EVANS, LITTLER, and PEMBERTON 44 have
glucagon does not interfere with the peripheral uptake llately described 4 uncontrolled young diabetics of glucose. The same conclusion may be drawn from with large livers in which an excess of glycogen was In 3 of them, after an infusion of glucagon : the experiments of HUBBLE,39 who found that the fall found. of the blood-sugar curve in 17 diabetics after an the blood-sugar rose only by 85, 20, and 35 mg. per injection of glucagon closely paralleled the fall seen in 100 ml.-a result attributed- by the investigators to the glucose-tolerance test of these same diabetics. Inimpaired glycogenolysis. One may assume that the 3 thyrotoxic diabetics, on the other hand, the blood-height of the fasting blood-sugar must have some sugar fall was faster after glucagon hyperglycsemia influence on the capacity of the liver to mobilise than after alimentary hyperglycoemia. VOLK et aL40 glycogen, and in these cases the fasting blood-sugars report a diminished insulin sensitivity in hyperthyroid were 425, 420, and 450 mg. per 100 ml. It would dogs, which they attribute to the rapid breakdown of have been valuable to have repeated the glucagon hepatic glycogen in the hyperthyroid state-a break- test after insulin, as in the child whose case is down faster than the uptake (also rapid) of glucose quoted above. Moreover, it has already been demonThe distinction between strated that in such uncontrolled cases, with glycogenat the periphery. glucagon and which filled livers, an injection of adrenaline provokes a alimentary hyperglycsemia hyperglycaemia HUBBLE observed in thyrotoxic diabetics could thus normal glycogenolytic response.45 Adrenaline (probe explained by glucagon having emptied the liver of vided it is not used in an impotent solution 46 47) its glycogen, leaving little to be mobilised later by remains both a more powerful and a more accessible thyroxine. VAN ITALLIE et a1.38and HuBBLE 39 exam- glycogenolytic agent than glucagon. ined the effect on the blood-sugar of glucagon given with an intramuscular injection of adrenaline. The Annotations blood-sugar curves were considerably higher than when NOBEL PRIZE IN MEDICINE glucagon alone was injected-from which HUBBLE infers that glucagon does not inhibit the glycogenoTHE award of the Nobel prize in physiology and lytic effect of adrenaline on muscle, whereas VAN medicine to Prof. Hugo Theorell of the Nobel Institute, ITTALIE and his colleagues conclude that adrenaline Stockholm, represents the second occasion on which inhibits peripheral glucose uptake. This conclusion this honour has been given to a compatriot of the they support by showing that the capillary-venous founder. Professor Theorell’s fundamental contribution to the differences in the blood-sugar were almost removed by of cell was made in the the action of adrenaline. Glucagon then is not an insulin-antagonist; its site of origin is still undetermined ; and its hormonal status is uncertain. Indeed, if it is a hormone it probably acts synergistically with insulin, by making hepatic glycogen available for insulin action at the periphery.4142 ANDERSON 43 has reviewed the experimental evidence which suggests that glucagon not only potentiates the action of insulin, but also stimulates its production during the postabsorptive period. If the place of glucagon in human physiology is still unsettled, its use in pathological diagnosis requires critical examination. KIRTLEY et al.32 used glucagon in 8 diabetics, and on the shape of the consequent blood-sugar curves they divided these diabetics into two groups. 4 who were young and thin, in whom the diabetes was labile and ketotic, showed a small rise and a rapid fall; while 4 elderly, obese, and non-ketotic diabetics showed a higher rise and a slow fall. By the response to glucagon, the well-known insulin-sensitive and insulin-insensitive types could thus be differentiated. But HUBBLE, having repeated this work and compared the results with the Himsworth insulin-glucose-tolerance test, the insulintolerance test, the glucose-tolerance test, and the patient’s clinical type, does not believe that any such differentiation is possible by the injection of glucagon. Several of his elderly and obese diabetics showed only a small rise (less than 25%) over the fasting bloodwhile in one child diabetic the response of the sugar, to was increased from 18 to 53% blood-sugar glucagon a meal and the test was made. insulin before by giving
39. Hubble, D. Diabetes, 1955, 4, 197. 40. Volk, B. W., Lazarus, S. S., Lew, H. Metabolism, 1955, 4, 10. 41. Pincus, I. J., Rutman, J. Z. Arch. intern. Med. 1953, 92, 666. 42. MacCrath, W. B., Snedecor, J. G. Diabetes, 1953, 2, 443. 43. Anderson, G. Science, 1955, 122, 457.
study
early ’thirties,
respiration
when he isolated the " yellow respiratory enzyme" in crystalline form. Other contemporaries-notably Otto Warburg, another Nobel prizeman-helped to define the chemical nature of this enzyme ; but to Theorell goes the credit for showing that the enzyme could be reversibly split into two inactive portionsnamely, a prosthetic group (riboflavine phosphate) and a protein carrier. This enzyme is now known as the " old yellow enzyme " to distinguish it from other yellow respiratory ferments that have since been discovered. Of late years Professor Theorell has added notably to our knowledge of oxidase enzymes of the cytochrome type. These enzymes are also associated with cell respiration and act in conjunction with the flavine enzymes. VASOMOTOR HEADACHE AND EPILEPSY THE borderlands of epilepsy constitute a perpetual diagnostic problem. At what stage, for instance, should we term " epileptic " the patient who repeatedly has sudden brief loss of consciousness, often with pallor and perhaps occasionally a little minor twitching, and In such cases whose attacks appear quite causeless considerable reliance has been placed on electroencephalography, which occasionally gives an unequivocal But as our knowledge of the range of normal answer. has increased the number of records regarded as decisive has been reduced, and we have been left increasingly to make a clinical decision. Heyck and Hess,48 working in Prof. H. Krayenbiihl’s clinic in Ziirich, seek to extend this borderland a little. They find that of 200 patients with severe episodic vasomotor headache 20 showed evidence of epileptic dysrhythmia in their electro-encephalograms, particularly after photic stimulationand of 48 patients with classical ’
44. Evans, R. W., Littler, T. R., Pemberton, H. S. J. clin. Path. 1955, 8, 10. 45. Houet, R. Pr. méd. 1949, 12, 159. 46. Crawford, T. Quart. J. Med. 1946, 15, 285. 47. Hubble, D. Lancet, 1954, i, 235 48. Heyck, von H., Hess, R. Schweiz. Med. Wschr. 1955, 85, 573.