Studies on insulin receptor in chronic renal failure
This study was undertaken to analyze the deteriorated glucose tolerance in chronic renal failure and to investigate the effects of various blood purification methods on glucose tolerance by examining the results of intravenous glucose tolerance tests (ivGTT) and insulin binding ability to mature ery...
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| Published in | Journal of Japanese Society for Dialysis Therapy Vol. 19; no. 2; pp. 183 - 197 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Japanese |
| Published |
The Japanese Society for Dialysis Therapy
1986
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 0911-5889 1884-6211 |
| DOI | 10.4009/jsdt1985.19.183 |
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| Abstract | This study was undertaken to analyze the deteriorated glucose tolerance in chronic renal failure and to investigate the effects of various blood purification methods on glucose tolerance by examining the results of intravenous glucose tolerance tests (ivGTT) and insulin binding ability to mature erythrocytes. Forty-two chronic renal failure patients, 11 undialyzed (UD), 22 hemodialyzed (HD) (10 acetate (HDA)-and 12 bicarbonate (HDB)-dialyzed) and 9 hemofiltrated (HF) patients, were chosen for this study. The UD patients showed deteriorated glucose tolerance, but both the HD and HF patients had improved glucose tolerance. 125I-insulin specific binding to erythrocytes from the UD patients was significantly lower than that for normal subjects, HD and HF patients. The HDA and HDB patients showed similar 125I-insulin specific binding to erythrocytes, which was significantly lower than that for normal subjects. However, there was no significant difference in the specific binding value between HF and normal subjects. From De Meyts analyses of the Scatchard plots, the unoccupied receptor site affinity constant, Ke, was determined to be as follows: normal subiects, 0.437×108M-1; UD, 0.650×108M-1; HD, 0.490×108M-1; HF, 0.345×108M-1. The numbers of insulin receptor sites per erythrocyte were as follows: normal subjects, 450; UD, 205; HD, 380; HF, 590. These results suggested that a decrease in the number of insulin receptor sites was responsible for the deteriorated glucose tolerance in chronic renal failure. Although the insulin-binding ability was impaired in HD patients, glucose tolerance was improved, which might be explained by compensation at the expense of insulin oversecretion. In HF patients, the insulin-binding ability was found to be normal, probably due to the increase in the number of insulin receptor sites. Therefore, HF may be a better blood purification method than HD for improving glucose tolerance in chronic renal failure. |
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| AbstractList | This study was undertaken to analyze the deteriorated glucose tolerance in chronic renal failure and to investigate the effects of various blood purification methods on glucose tolerance by examining the results of intravenous glucose tolerance tests (ivGTT) and insulin binding ability to mature erythrocytes. Forty-two chronic renal failure patients, 11 undialyzed (UD), 22 hemodialyzed (HD) (10 acetate (HDA)-and 12 bicarbonate (HDB)-dialyzed) and 9 hemofiltrated (HF) patients, were chosen for this study. The UD patients showed deteriorated glucose tolerance, but both the HD and HF patients had improved glucose tolerance. 125I-insulin specific binding to erythrocytes from the UD patients was significantly lower than that for normal subjects, HD and HF patients. The HDA and HDB patients showed similar 125I-insulin specific binding to erythrocytes, which was significantly lower than that for normal subjects. However, there was no significant difference in the specific binding value between HF and normal subjects. From De Meyts analyses of the Scatchard plots, the unoccupied receptor site affinity constant, Ke, was determined to be as follows: normal subiects, 0.437×108M-1; UD, 0.650×108M-1; HD, 0.490×108M-1; HF, 0.345×108M-1. The numbers of insulin receptor sites per erythrocyte were as follows: normal subjects, 450; UD, 205; HD, 380; HF, 590. These results suggested that a decrease in the number of insulin receptor sites was responsible for the deteriorated glucose tolerance in chronic renal failure. Although the insulin-binding ability was impaired in HD patients, glucose tolerance was improved, which might be explained by compensation at the expense of insulin oversecretion. In HF patients, the insulin-binding ability was found to be normal, probably due to the increase in the number of insulin receptor sites. Therefore, HF may be a better blood purification method than HD for improving glucose tolerance in chronic renal failure. |
| Author | Esaki, Kazuyoshi |
| Author_xml | – sequence: 1 fullname: Esaki, Kazuyoshi organization: Department of Urology, Osaka City University Medical School |
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| References | 3) Hampers, C. L., Lowrie, E. G., Soeldner, J. S. and Merrill, J. P.: The effect of uremia upon glucose metabolism. Arch. Intern. Med., 126: 870-874, 1970. 15) Hunter, W. M. and Greenwood, F. C.: Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature, 194: 495-496, 1962. 34) Soman, V. and Felig, P.: Glucagon and insulin binding to liver membranes in a partially nephrectomized uremic rat model. J. Clin. Invest., 60: 224-232, 1977. 13) 小林 正, 岩崎 誠, 前川 聡, 繁田幸男: ラット赤血球と脂肪細胞のインスリンレセプターの相関. 糖尿病, 23: 743-749, 1980. 12) Ganbhir, K. K., Archer, J. A. and Bradley, C. J.: Characteristics of human erythrocyte insulin receptors. Diabetes, 27: 701-708, 1980. 20) 金井 泉, 金井正光: 血液化学検査法, 臨床検査法提要, 改訂28版, VII 1-138, 金原出版, 東京, 1978. 36) 水谷洋子, 山本忠司, 野崎寛爾, 山川 真, 岸本武利, 前川正信: 血液透析中の酢酸の影響と重炭酸透析について. 透析会誌, 13: 539-545, 1980. 30) Dzúrik, R. and Brixová, E.: Liver glycogen concentration in patients with chronic uremia. Experientia, 24: 552-553, 1968. 7) Yamagami, S., Ezaki, K., Sugimura, K., Tanaka, H., Kishimoto, T. and Maekawa, M.: Quantitative analysis of abnormal glucose metabolism. 人口臓器, 10: 945-948, 1981. 28) Muggeo, M., Bar, R. S., Roth, J., Kahn, C. R. and Gorden, P.: The insulin resistance of acromegaly: Evidence for two alterations in the insulin receptor on circulating monocytes. J. Clin. Endocrinol. Metab., 48: 17-25, 1979. 43) 山上征二, 岸本武利: 血液濾過法のkinetics. 新しい血液浄化法. 南江堂, 東京, p. 25-35, 1981. 31) Bar, R. S., Gorden, P., Roth, J. and Siebert, C. W.: Insulin receptors in patients insulinomas: Changes in receptor affinity and concentration. J. Clin. Endocrinol. Metab., 44: 1210-1213, 1977. 33) 繁田幸男: インスリンレセプターをめぐる最近の知見. 最新医学, 37: 54-59, 1982. 27) Olefsky, J. M. and Reaven, G. M.: Insulin binding in diabetes: Relationships with plasma insulin levels and insulin sensitivity. Diabetes, 26: 680-688, 1977. 35) 安田圭吾, Kitabchi, A. E: 糖尿病性アチドーシスにおける赤血球インスリン結合能. 糖尿病, 25: 433, 1982. 37) 山上征二, 泉 暢英, 吉本 忍, 岸本武利, 前川正信, 古川 望: hemofiltrationに関する研究 (第3報) -HF用Filterの評価と専用膜の開発-腎と透析, 7: 103-108, 1979. 14) 前川正信, 岸本武利, 山上征二, 吉本 忍, 田中 寛, 山川 眞, 太田宗喜: 濾過型人工腎臓の基礎と臨床. 医学のあゆみ, 105: 514-521, 1978. 18) De Meyts, P. and Roth, J.: Cooperativity in ligand binding: A new graphic analysis. Biochem. Biophys. Res. Commun., 66: 1118-1126, 1975. 41) Kishioto, T., Yamagami, S., Tanaka, H., Ohyama, T., Yamamoto, T., Yamakawa, M., Nishino, M., Yoshimoto, S. and Maekawa, M.: Superiority of hemofiltration to hemodialysis for treatment of chronic renal failure: Comparative stadies between hemofiltration and hemodailysis on dialysis disequibrium syndrome. Artif. Organs, 4: 86-93, 1980. 42) Whittaker, J., Cuthbert, C., Hammond, V. A. and Alberti, K. G. M. M.: The effects of metabolic acidosis in vivo on insulin binding to isolated rat adipocytes. Metabolism, 31: 553-557, 1982. 5) DeFronzo, R. A., Tobin, J. D., Rowe, J. W. and Andres, R.: Glucose intolerance in uremia: Quantification of pancreatic beta cell sensitivity to glucose and tissue sensitivity to insulin. J. Clin. Invest., 62: 425-435, 1978. 8) Bar, R. S., Gorden, P., Roth, J., Kahn, C. R. and DeMeyts, P.: Fluctuations in the affinity and concentration of insulin receptors on circulating monocytes of obese patients. J. Clin. Invest., 58: 1123-1135, 1976. 23) 宮本 力, 杉原幹人, 西村治雄: Solid phase radioimmunoassay kit (phadebas insulin test) による血中インスリン測定の基礎的検討. 基礎と臨床, 6: 1439-1448, 1972. 11) Milutinovic, S, breyer, D., Jankovic, M., Stefovic, A., Molnar, V., Mrzljak, V. and Rocic, B.: Improvement of insulin binding to erythrocyte insulin receptors in uraemia by hæmodialysis. Proc EDTA, 19: 763-768, 1982. 17) Scatchard, G.: The attractions of proteins for small molecules and ions. Ann. N.Y. Acad. Sci., 51: 660-672, 1949. 1) Hunchings, R. H., Hegstrom, R. M. and Scribner, B. H.: Glucose intolerance in patients on long-term intermittent dialysis. Ann. Intern. Med., 65: 275-285, 1966. 26) Hous, P. D. R. and Weidemann, M. J.: Characterization of an 125I-insulin binding plasma membrane fraction from rat liver. Biochem. Biophys. Res. Commun., 41: 541-548, 1970. 16) Freychet, P., Roth, J. and Neville, D. M., Jr.: Monoiode-insulin: Demonstration of its biological activity and binding to fat cells and liver membranes. Biochem. Biophys. Res. Commun., 43: 400-408, 1971. 4) Briggs, J. D., Buchanan, K. D., Luke, R. G. and Mckiddie, M. T.: Role of insulin in glucose intolerance in uraemia. Lancet, 1: 462-464, 1967. 38) 秋葉 隆: ホルモンと濾過型人工腎. 新しい血液浄化法, 南江堂, 東京, p. 99-104, 1981. 29) Davidoson, M. B., Lowrie, E. G, and Humpers, C. L.: Lack of dialyzable insulin antagonist in uremia. Metabolism, 18: 387-394, 1969. 10) Gambhir, K. K., Archer, J. A., Nerurkar, S. G., Cruz, I. A, and Sanders, M.: Erythrocyte insulin receptors in chronic renal failure. Nephron, 28: 4-10, 1981. 25) Cuatrecasas, P.: Interaction of insulin with the cell membrane: The primary action of insulin. Proc. N. A. S., 63: 450-457, 1969. 6) 金田 浩, 村田豊明, 三村信英: 糖代謝異常. 日本臨床, 39 (No. 474): 148-158, 1981. 22) Brecher, G.: New methylene blue as a reticulocyte stain. Am. J. Clin. Path., 19: 895-896, 1949. 2) Horton, E. S., Johnson, C. and Lebovitz, H. E.: Carbohydrate metabolism in uremia. Ann. Intern. Med., 68: 63-74, 1968. 21) Eng, J., Lee, L. and Yalow, R. S.: Influence of the age of erythrocytes on their insulin receptors. Diabetes, 29: 164-166. 1980. 24) Berson, S. A. and Yalow, R. S.: Quantitative aspects of the reaction between insulin and insulin-binding antibody. J. Clin. Invest., 38: 1996-2016, 1959. 39) Lindall, A., Carmena, R., Cohen, S. and Comty, C.: Insulin hypersecretion in patients on chronic hemodialysis: Role of parathyroids. J. Clin. Endocr., 32: 653-658, 1971. 32) Wachslicht-Rodbard, H., Gross, H. A., Rodbard, D., Ebert, M. H. and Roth, J.: Increased insulin binding to erythrocytes in anorexia nervosa: Restoration to normal with refeeding. New. Engl. J. Med., 300: 882-887, 1979. 19) Lundbaek, K.: Intravenous glucose tolerance as a tool in definition and diagnosis of diabetes mellitus. Brit. Med. J., 2: 1507-1513, 1962. 9) Harrison, L. C., Martin, F. I. R. and Melick, R. A.: Correlation between insulin receptor binding in isolated fat cells and insulin sensity in obese human subjects. J. Clin. Invest., 58: 1435-1441, 1976. 40) Kramer, P., Matthaei, D., Fuchs, C. Arnold, R., Ebert, R., McIntosh, C., Schauder, P., Schwinn, G., Scheler, F., Ludwig, H. and Spitteler, G.: Assessment of hormone loss through hemofiltration. Artif. Organs, 2: 128-130, 1978. |
| References_xml | – reference: 32) Wachslicht-Rodbard, H., Gross, H. A., Rodbard, D., Ebert, M. H. and Roth, J.: Increased insulin binding to erythrocytes in anorexia nervosa: Restoration to normal with refeeding. New. Engl. J. Med., 300: 882-887, 1979. – reference: 41) Kishioto, T., Yamagami, S., Tanaka, H., Ohyama, T., Yamamoto, T., Yamakawa, M., Nishino, M., Yoshimoto, S. and Maekawa, M.: Superiority of hemofiltration to hemodialysis for treatment of chronic renal failure: Comparative stadies between hemofiltration and hemodailysis on dialysis disequibrium syndrome. Artif. Organs, 4: 86-93, 1980. – reference: 19) Lundbaek, K.: Intravenous glucose tolerance as a tool in definition and diagnosis of diabetes mellitus. Brit. Med. J., 2: 1507-1513, 1962. – reference: 42) Whittaker, J., Cuthbert, C., Hammond, V. A. and Alberti, K. G. M. M.: The effects of metabolic acidosis in vivo on insulin binding to isolated rat adipocytes. Metabolism, 31: 553-557, 1982. – reference: 5) DeFronzo, R. A., Tobin, J. D., Rowe, J. W. and Andres, R.: Glucose intolerance in uremia: Quantification of pancreatic beta cell sensitivity to glucose and tissue sensitivity to insulin. J. Clin. Invest., 62: 425-435, 1978. – reference: 22) Brecher, G.: New methylene blue as a reticulocyte stain. Am. J. Clin. Path., 19: 895-896, 1949. – reference: 10) Gambhir, K. K., Archer, J. A., Nerurkar, S. G., Cruz, I. A, and Sanders, M.: Erythrocyte insulin receptors in chronic renal failure. Nephron, 28: 4-10, 1981. – reference: 12) Ganbhir, K. K., Archer, J. A. and Bradley, C. J.: Characteristics of human erythrocyte insulin receptors. Diabetes, 27: 701-708, 1980. – reference: 28) Muggeo, M., Bar, R. S., Roth, J., Kahn, C. R. and Gorden, P.: The insulin resistance of acromegaly: Evidence for two alterations in the insulin receptor on circulating monocytes. J. Clin. Endocrinol. Metab., 48: 17-25, 1979. – reference: 3) Hampers, C. L., Lowrie, E. G., Soeldner, J. S. and Merrill, J. P.: The effect of uremia upon glucose metabolism. Arch. Intern. Med., 126: 870-874, 1970. – reference: 43) 山上征二, 岸本武利: 血液濾過法のkinetics. 新しい血液浄化法. 南江堂, 東京, p. 25-35, 1981. – reference: 6) 金田 浩, 村田豊明, 三村信英: 糖代謝異常. 日本臨床, 39 (No. 474): 148-158, 1981. – reference: 13) 小林 正, 岩崎 誠, 前川 聡, 繁田幸男: ラット赤血球と脂肪細胞のインスリンレセプターの相関. 糖尿病, 23: 743-749, 1980. – reference: 21) Eng, J., Lee, L. and Yalow, R. S.: Influence of the age of erythrocytes on their insulin receptors. Diabetes, 29: 164-166. 1980. – reference: 38) 秋葉 隆: ホルモンと濾過型人工腎. 新しい血液浄化法, 南江堂, 東京, p. 99-104, 1981. – reference: 27) Olefsky, J. M. and Reaven, G. M.: Insulin binding in diabetes: Relationships with plasma insulin levels and insulin sensitivity. Diabetes, 26: 680-688, 1977. – reference: 14) 前川正信, 岸本武利, 山上征二, 吉本 忍, 田中 寛, 山川 眞, 太田宗喜: 濾過型人工腎臓の基礎と臨床. 医学のあゆみ, 105: 514-521, 1978. – reference: 17) Scatchard, G.: The attractions of proteins for small molecules and ions. Ann. N.Y. Acad. Sci., 51: 660-672, 1949. – reference: 8) Bar, R. S., Gorden, P., Roth, J., Kahn, C. R. and DeMeyts, P.: Fluctuations in the affinity and concentration of insulin receptors on circulating monocytes of obese patients. J. Clin. Invest., 58: 1123-1135, 1976. – reference: 31) Bar, R. S., Gorden, P., Roth, J. and Siebert, C. W.: Insulin receptors in patients insulinomas: Changes in receptor affinity and concentration. J. Clin. Endocrinol. Metab., 44: 1210-1213, 1977. – reference: 37) 山上征二, 泉 暢英, 吉本 忍, 岸本武利, 前川正信, 古川 望: hemofiltrationに関する研究 (第3報) -HF用Filterの評価と専用膜の開発-腎と透析, 7: 103-108, 1979. – reference: 20) 金井 泉, 金井正光: 血液化学検査法, 臨床検査法提要, 改訂28版, VII 1-138, 金原出版, 東京, 1978. – reference: 29) Davidoson, M. B., Lowrie, E. G, and Humpers, C. L.: Lack of dialyzable insulin antagonist in uremia. Metabolism, 18: 387-394, 1969. – reference: 2) Horton, E. S., Johnson, C. and Lebovitz, H. E.: Carbohydrate metabolism in uremia. Ann. Intern. Med., 68: 63-74, 1968. – reference: 7) Yamagami, S., Ezaki, K., Sugimura, K., Tanaka, H., Kishimoto, T. and Maekawa, M.: Quantitative analysis of abnormal glucose metabolism. 人口臓器, 10: 945-948, 1981. – reference: 23) 宮本 力, 杉原幹人, 西村治雄: Solid phase radioimmunoassay kit (phadebas insulin test) による血中インスリン測定の基礎的検討. 基礎と臨床, 6: 1439-1448, 1972. – reference: 26) Hous, P. D. R. and Weidemann, M. J.: Characterization of an 125I-insulin binding plasma membrane fraction from rat liver. Biochem. Biophys. Res. Commun., 41: 541-548, 1970. – reference: 33) 繁田幸男: インスリンレセプターをめぐる最近の知見. 最新医学, 37: 54-59, 1982. – reference: 39) Lindall, A., Carmena, R., Cohen, S. and Comty, C.: Insulin hypersecretion in patients on chronic hemodialysis: Role of parathyroids. J. Clin. Endocr., 32: 653-658, 1971. – reference: 34) Soman, V. and Felig, P.: Glucagon and insulin binding to liver membranes in a partially nephrectomized uremic rat model. J. Clin. Invest., 60: 224-232, 1977. – reference: 24) Berson, S. A. and Yalow, R. S.: Quantitative aspects of the reaction between insulin and insulin-binding antibody. J. Clin. Invest., 38: 1996-2016, 1959. – reference: 1) Hunchings, R. H., Hegstrom, R. M. and Scribner, B. H.: Glucose intolerance in patients on long-term intermittent dialysis. Ann. Intern. Med., 65: 275-285, 1966. – reference: 25) Cuatrecasas, P.: Interaction of insulin with the cell membrane: The primary action of insulin. Proc. N. A. S., 63: 450-457, 1969. – reference: 18) De Meyts, P. and Roth, J.: Cooperativity in ligand binding: A new graphic analysis. Biochem. Biophys. Res. Commun., 66: 1118-1126, 1975. – reference: 36) 水谷洋子, 山本忠司, 野崎寛爾, 山川 真, 岸本武利, 前川正信: 血液透析中の酢酸の影響と重炭酸透析について. 透析会誌, 13: 539-545, 1980. – reference: 4) Briggs, J. D., Buchanan, K. D., Luke, R. G. and Mckiddie, M. T.: Role of insulin in glucose intolerance in uraemia. Lancet, 1: 462-464, 1967. – reference: 9) Harrison, L. C., Martin, F. I. R. and Melick, R. A.: Correlation between insulin receptor binding in isolated fat cells and insulin sensity in obese human subjects. J. Clin. Invest., 58: 1435-1441, 1976. – reference: 16) Freychet, P., Roth, J. and Neville, D. M., Jr.: Monoiode-insulin: Demonstration of its biological activity and binding to fat cells and liver membranes. Biochem. Biophys. Res. Commun., 43: 400-408, 1971. – reference: 11) Milutinovic, S, breyer, D., Jankovic, M., Stefovic, A., Molnar, V., Mrzljak, V. and Rocic, B.: Improvement of insulin binding to erythrocyte insulin receptors in uraemia by hæmodialysis. Proc EDTA, 19: 763-768, 1982. – reference: 15) Hunter, W. M. and Greenwood, F. C.: Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature, 194: 495-496, 1962. – reference: 40) Kramer, P., Matthaei, D., Fuchs, C. Arnold, R., Ebert, R., McIntosh, C., Schauder, P., Schwinn, G., Scheler, F., Ludwig, H. and Spitteler, G.: Assessment of hormone loss through hemofiltration. Artif. Organs, 2: 128-130, 1978. – reference: 35) 安田圭吾, Kitabchi, A. E: 糖尿病性アチドーシスにおける赤血球インスリン結合能. 糖尿病, 25: 433, 1982. – reference: 30) Dzúrik, R. and Brixová, E.: Liver glycogen concentration in patients with chronic uremia. Experientia, 24: 552-553, 1968. |
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| Title | Studies on insulin receptor in chronic renal failure |
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