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INSULIN ANTAGONISM IN HUMAN SERUM
831 course, the
liver-biopsy findings, I am sure, have not been influenzce infection, so probably the finding of reported this organism is fortuitous. On the other hand, it does seem rather an obvious finding that I think should be commented on. as
H.
Department of Pædiatrics, University of Western Ontario Faculty of Medicine, London, Canada.
L. L.
DE
VEBER.
diabetic patients are used; a quantitative estimation can be obtained by measuring the angle formed by the two lines (see figure). The mean values of glucose uptake obtained with different insulin concentrations and progressive dilution of the sera are shown in the accompanying table. The slope (b) for each set of experiments has been calculated and the width of the angle e has been obtained from the formula tan
INSULIN ANTAGONISM IN HUMAN SERUM
SiR,ňOne of the main drawbacks of serum-insulin bioassay is the so-called augmentation phenomenon, which results in apparent increase of insulin activity upon serum dilution. A result of this phenomenon is that when different concentrations of the sample are plotted against the metabolic response which is studied, the line is no longer parallel to that obtained with different concentrations of the insulin standards. The figure shows the results obtained with sera from normal subjects.
e8
=
b1- b2 bi b2 + 1
where bi is the slope of the insulin standards and b2 the slope of serum-dilutions. The difference between normals and diabetics is statistically significant. These data suggest the presence of a factor (or factors) in human serum which interferes with serum insulin-like activity. The concentration of this factor(s) diabetic than in normal sera. Istituto di Clinica Medica Generale di Terapia Medica, University of Milan, Italy.
seems
to
be
higher
in
GUIDO POZZA ALBERTO GHIDONI.
ASPIRIN, VITAMIN-C DEFICIENCY,
AND GASTRIC HÆMORRHAGE SiR,ňThe report by Dr. Russell and colleagues (Sept. 14, p. 603) suggests that aspirin initiates gastrointestinal heemorrhage in individuals who are deficient in vitamin C. It also seems that this was particularly so for bleeding from acute gastric lesions (erosions) in elderly people. These observations are of considerable interest in relation to the mechanism of
Glucose uptake by rat epididymal fat-pad in presence of increasing concentrations of insulin (continuous line) and progressive dilutions of serum (interrupted lines) of normal and diabetic
patients.
It seems that glucose uptake, plotted against the logarithm of different serum-dilutions, is not parallel to the insulin-standard curve; in other words, upon dilution of the serum an augmentation effect of its insulin-like activity, expressed as glucose uptake by rat epididymal fat-pad, becomes apparent. (Insulin bioassay was carried out by the pooled " rat epididymal-fatpad method according to Froesch et al.1 Glucose uptake was determined as metabolic index. The method has been fully described.2) Similar findings have been reported by several other workers,2-6 and recently stressed by Powers et al.7-9 This phenomenon is much more evident when sera of "
1. 2. 3. 4. 5. 6. 7. 8. 9.
aspirin-induced gastric bleeding. When aspirin is left in contact with human gastric mucosa for a few minutes it causes a sharp increase in the rate of exfoliation of gastric epithelial cells. 12 It has been suggested that this effect may initiate the formation of gastric erosions.8 Normally, the replacement (or turnover) of gastric surface epithelial cells is rapid,4 which is presumably why the mucosa heals in a few days after the ingestion of irritants.Thus, it can be argued that human gastric mucosa does not usually bleed overtly after aspirin ingestion because the mucosa protects itself by responding to an excessive loss of epithelial cells with an increased rate of cell production. In support of this explanation is the evidence that individuals with a higher-than-normal turnover of gastric epithelium bleed less after aspirin.6 Gastric mucosa unable to increase its rate of cell production might be expected to bleed more after aspirin ingestion.’ The patients investigated by Dr. Russell and his colleagues were deficient in vitamin C, but these workers do not state if they were also deficient in other nutrients, which may be defective in association with vitamin-C deficiency.119 Folic acid is of importance in this regard, for this vitamin is required for normal cell division. If the gastric mucosa of their patients was malnourished and unable to respond to an aspirin-induced loss of epithelial cells by an increased production of epithelial
Froesch, E. R., Bürgi, H., Ramseier, E. B., Bally, P., Labhart, A. J. clin. Invest. 1963, 42, 1816. Pozza, G., Ghidoni, A., Sanesi, E. Metabolismo, 1966, 4, 305. Sheps, M. G., Nickerson, R. J., Dagenais, Y. M., Steinke, J., Martin, D. B., Renold, A. E. J. clin. Invest. 1960, 39, 1499. Ball, E. G., Merril, M. A. Endocrinology, 1961, 69, 596. Lyngsoe, J. Acta med. scand. 1962, 171, 365. Power, L., Lucas, C., Conn, J. Diabetes, 1965, 14, 11. Power, L., Rojas, G. R., Londono, J. H. Lancet, 1967, i, 1123. Power, L. ibid. p. 1138. Power, L., Shuman, J. Diabetes, 1967, 16, 483.
GLUCOSE UPTAKE
(mg.
PER
g.
PER
hr.
±S.D.)
DIABETIC
1. 2. 3. 4. 5. 6.
Groft, D. N. Br. med. J.1963, ii, 897. Horwich, L., Evans, D. A. P. Gut, 1966, 7, 525. Croft, D. N. J. Pharm. Pharmac. 1966, 18, 354. Stevens, C. E., Leblond, C. P. Anat. Rec. 1953, 115, 231. Palmer, E. D. Medicine, Baltimore, 1954, 33, 199. Croft, D. N., Wood, P. H. N. Br. med. J. 1967, i, 137. 7. Croft, D. N. D.M. thesis, University of Oxford, 1966. 8. Read, A. E., Gough, K. R., Pardoe, J. L., Nicholas, A. Br. med. J. 1965, ii, 843. 9. Batata, M., Spray, G. H., Bolton, F. C., Higgins, G., Wollner, L. ibid. 1967, i, 667.
BY RAT EPIDIDYMAL FAT-PAD IN PROGRESSIVELY DILUTED SERUM FROM NORMAL AND
PATIENTS, COMPARED
WITH INSULIN STANDARDS
liver-biopsy findings, I am sure, have not been influenzce infection, so probably the finding of reported this organism is fortuitous. On the other hand, it does seem rather an obvious finding that I think should be commented on. as
H.
Department of Pædiatrics, University of Western Ontario Faculty of Medicine, London, Canada.
L. L.
DE
VEBER.
diabetic patients are used; a quantitative estimation can be obtained by measuring the angle formed by the two lines (see figure). The mean values of glucose uptake obtained with different insulin concentrations and progressive dilution of the sera are shown in the accompanying table. The slope (b) for each set of experiments has been calculated and the width of the angle e has been obtained from the formula tan
INSULIN ANTAGONISM IN HUMAN SERUM
SiR,ňOne of the main drawbacks of serum-insulin bioassay is the so-called augmentation phenomenon, which results in apparent increase of insulin activity upon serum dilution. A result of this phenomenon is that when different concentrations of the sample are plotted against the metabolic response which is studied, the line is no longer parallel to that obtained with different concentrations of the insulin standards. The figure shows the results obtained with sera from normal subjects.
e8
=
b1- b2 bi b2 + 1
where bi is the slope of the insulin standards and b2 the slope of serum-dilutions. The difference between normals and diabetics is statistically significant. These data suggest the presence of a factor (or factors) in human serum which interferes with serum insulin-like activity. The concentration of this factor(s) diabetic than in normal sera. Istituto di Clinica Medica Generale di Terapia Medica, University of Milan, Italy.
seems
to
be
higher
in
GUIDO POZZA ALBERTO GHIDONI.
ASPIRIN, VITAMIN-C DEFICIENCY,
AND GASTRIC HÆMORRHAGE SiR,ňThe report by Dr. Russell and colleagues (Sept. 14, p. 603) suggests that aspirin initiates gastrointestinal heemorrhage in individuals who are deficient in vitamin C. It also seems that this was particularly so for bleeding from acute gastric lesions (erosions) in elderly people. These observations are of considerable interest in relation to the mechanism of
Glucose uptake by rat epididymal fat-pad in presence of increasing concentrations of insulin (continuous line) and progressive dilutions of serum (interrupted lines) of normal and diabetic
patients.
It seems that glucose uptake, plotted against the logarithm of different serum-dilutions, is not parallel to the insulin-standard curve; in other words, upon dilution of the serum an augmentation effect of its insulin-like activity, expressed as glucose uptake by rat epididymal fat-pad, becomes apparent. (Insulin bioassay was carried out by the pooled " rat epididymal-fatpad method according to Froesch et al.1 Glucose uptake was determined as metabolic index. The method has been fully described.2) Similar findings have been reported by several other workers,2-6 and recently stressed by Powers et al.7-9 This phenomenon is much more evident when sera of "
1. 2. 3. 4. 5. 6. 7. 8. 9.
aspirin-induced gastric bleeding. When aspirin is left in contact with human gastric mucosa for a few minutes it causes a sharp increase in the rate of exfoliation of gastric epithelial cells. 12 It has been suggested that this effect may initiate the formation of gastric erosions.8 Normally, the replacement (or turnover) of gastric surface epithelial cells is rapid,4 which is presumably why the mucosa heals in a few days after the ingestion of irritants.Thus, it can be argued that human gastric mucosa does not usually bleed overtly after aspirin ingestion because the mucosa protects itself by responding to an excessive loss of epithelial cells with an increased rate of cell production. In support of this explanation is the evidence that individuals with a higher-than-normal turnover of gastric epithelium bleed less after aspirin.6 Gastric mucosa unable to increase its rate of cell production might be expected to bleed more after aspirin ingestion.’ The patients investigated by Dr. Russell and his colleagues were deficient in vitamin C, but these workers do not state if they were also deficient in other nutrients, which may be defective in association with vitamin-C deficiency.119 Folic acid is of importance in this regard, for this vitamin is required for normal cell division. If the gastric mucosa of their patients was malnourished and unable to respond to an aspirin-induced loss of epithelial cells by an increased production of epithelial
Froesch, E. R., Bürgi, H., Ramseier, E. B., Bally, P., Labhart, A. J. clin. Invest. 1963, 42, 1816. Pozza, G., Ghidoni, A., Sanesi, E. Metabolismo, 1966, 4, 305. Sheps, M. G., Nickerson, R. J., Dagenais, Y. M., Steinke, J., Martin, D. B., Renold, A. E. J. clin. Invest. 1960, 39, 1499. Ball, E. G., Merril, M. A. Endocrinology, 1961, 69, 596. Lyngsoe, J. Acta med. scand. 1962, 171, 365. Power, L., Lucas, C., Conn, J. Diabetes, 1965, 14, 11. Power, L., Rojas, G. R., Londono, J. H. Lancet, 1967, i, 1123. Power, L. ibid. p. 1138. Power, L., Shuman, J. Diabetes, 1967, 16, 483.
GLUCOSE UPTAKE
(mg.
PER
g.
PER
hr.
±S.D.)
DIABETIC
1. 2. 3. 4. 5. 6.
Groft, D. N. Br. med. J.1963, ii, 897. Horwich, L., Evans, D. A. P. Gut, 1966, 7, 525. Croft, D. N. J. Pharm. Pharmac. 1966, 18, 354. Stevens, C. E., Leblond, C. P. Anat. Rec. 1953, 115, 231. Palmer, E. D. Medicine, Baltimore, 1954, 33, 199. Croft, D. N., Wood, P. H. N. Br. med. J. 1967, i, 137. 7. Croft, D. N. D.M. thesis, University of Oxford, 1966. 8. Read, A. E., Gough, K. R., Pardoe, J. L., Nicholas, A. Br. med. J. 1965, ii, 843. 9. Batata, M., Spray, G. H., Bolton, F. C., Higgins, G., Wollner, L. ibid. 1967, i, 667.
BY RAT EPIDIDYMAL FAT-PAD IN PROGRESSIVELY DILUTED SERUM FROM NORMAL AND
PATIENTS, COMPARED
WITH INSULIN STANDARDS