Summary
The insulin binding properties and the molecular weights of the insulin receptor and its insulin binding subunit were studied in omental and subcutaneous adipocytes prepared from obese- and normal-weight subjects. Insulin binding by such adipocytes was decreased in obesity when the binding activity was expressed per unit of cell surface area. No significant difference from the lean controls was evident, however, when binding was calculated on a per cell basis, indicating that the total receptor content of the cells from the obese subjects was not altered. In addition, the normal difference in the receptor binding affinities previously reported between omental and subcutaneous cells from lean individuals was unaffected by the obese condition. Studies of the molecular weight of the non-reduced insulin receptor in fat cell membranes prepared from pieces of omental and subcutaneous fat demonstrated a major receptor species of 390–425K Mr. In contrast, adipocytes isolated by collagenase treatment of the fat had heterogenous non-reduced receptor species of Mr 355K, 285K and small amounts of 427K and 182K. Although different non-reduced receptor species were evident depending on the adipocyte receptor preparation (e.g. isolated adipocytes or fat cell membranes), no differences were found between obese and lean controls or between subcutaneous and omental receptors when the appropriate comparisons were made. Upon sulphydryl reduction, all receptor preparations had a major binding subunit of 125K Mr. In conclusion, obesity is characterized by a dilution of the insulin receptor over the adipocyte cell surface in the absence of a change in total cellular content of receptors. The difference in insulin binding affinities between omental and subcutaneous adipocytes could not be explained by an alteration in receptor molecular weight.
Article PDF
Similar content being viewed by others
References
Kreisberg R, Boshell B, DiPlacido J, Roddman R (1967) Insulin secretion in obesity. N Engl J Med 276: 314–319
Olefsky J (1981) Insulin resistance and insulin action. Diabetes 30: 148–162
Olefsky J (1976) Decreased insulin binding to adipocytes and circulating monocytes in obesity. J Clin Invest 57: 1165–1172
Kolterman O, Reaven G, Olefsky J (1979) Relationship between in vivo insulin resistance and decreased insulin receptors in obese man. J Clin Endocrinol Metab 48: 487–494
Harrison L, Martin F, Melick R (1976) Correlation between insulin receptor binding in isolated fat cells and insulin sensitivity in obese human subjects. J Clin Invest 58: 1435–1441
Kolterman O, Insel J, Saekow M, and Olefsky J (1980) Mechanisms of insulin resistance in human obesity. J Clin Invest 65: 1272–1284
Amatruda M, Livingston J, Lockwood D (1975) Insulin receptor: role in the resistance of human obesity to insulin. Science 188: 264–266
Pedersen O, Hijollunk E, Schwartz N (1982) Insulin receptor binding and insulin action in human fat cells: effects of obesity and fasting. Metabolism 31: 884–895
Lönnroth P, DiGirolamo M, Krotkiewski M, Smith U (1983) Insulin binding and responsiveness in fat cells from patients with reduced glucose tolerance and type II diabetes. Diabetes 32: 748–754
Borkan G, Cerzof S, Robbins A, Hults D, Silbert C, Silbert J (1982) Assessment of abdominal fat content by computed tomography. Am J Clin Nutr 36: 172–177
Bolinder J, Kager L, Östman J, Arner P (1983) Differences at the receptor and postreceptor levels between human omental and subcutaneous adipose tissue in the action of insulin on lipolysis. Diabetes 32: 117–123
Sjöstrom L, Björntorp P, Vrana J (1971) Microscopic fat cells: size measurements on frozen adipose tissue in comparison with automatic determinations of osimum-fixed fat cells. J Lipid Res 12: 521–530
Hirsch J, Gallian E (1968) Method for the determinations of adipose cell size and cell number in man and animals. J Lipid Res 9: 110–119
Zinder Z, Shapiro B (1971) Effect of cell size on epinephrine- and ACTH-induced fatty acid release from isolated fat cells. J Lipid Res 12: 91–95
Rodbell M (1964) Metabolism of isolated fat cells. I. Effects of hormone on glucose metabolism and lipolysis. J Biol Chem 239: 375–380
Belsham G, Denton R, Tanner M (1980) Use of novel rapid preparation of fat-cell plasma membranes employing Percoll to investigate the effects of insulin and adrenaline on membrane protein phosphorylation within intact fat-cells. Biochem J 192: 457–467
Gliemann J, Sonne O (1978) Binding and receptor-mediated degradation of insulin in adipocytes. J Biol Chem 253: 7857–7863
Scatchard G (1949) The attraction of protein for small molecules and ions. Ann NY Acad Sci 51: 660–672
Pilch P, Czech M (1979) Interaction of cross-linking agents with the insulin effector system of isolated fat cells. J Biol Chem 254: 3375–3381
Weber K, Pringle J, Osborn M (1972) Measurement of molecular weights by electrophoresis on SDS-acrylamide gel. Methods Enzymol 26: 3–27
Laemmli U (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685
Livingston J, Purvis B (1980) Effects of wheat germ agglutinin on insulin binding and insulin sensitivity of fat cells. Am J Physiol 238: E267-E275
Lerea K, Livingston J (1983) The different receptor species of liver have similar complex insulin binding properties. Biochem Biophys Res Commun 114: 1042–1047
Massague J, Pilch P, Czech M (1980) Electrophoretic resolution of three major insulin-receptor structures with unique subunit stoichiometries. Proc Natl Acad Sci (USA) 77: 7137–7141
Ciaraldi T, Kolterman O, Olefsky J (1981) Mechanism of the postreceptor defect in insulin action in human obesity. J Clin Invest 68: 875–880
Arner P, Bolinder J, Engfeldt P, Ostman J (1981) The antilipolytic effect of insulin in human adipose tissue in obesity, diabetes mellitus, hyperinsulinemia, and starvation. Metabolism 30: 753–760
Massague J, Pilch P, Czech M (1981) A unique proteolytic cleavage site on the β subunit of the insulin receptor. J Biol Chem 256: 3182–3190
Berhanu P, Kolterman O, Baron A, Tsai P, Olefsky J, Brandenburg D (1983) Insulin receptors in isolated human adipocytes. Characterization by photoaffinity labeling and evidence for internalization and cellular processing. J Clin Invest 72: 1958–1970
Rodbell, M (1964) Localization of lipoprotein lipase in fat cells of rat adipose tissue. J Biol Chem 239: 753–755
Mott D, Howard B, Bennett P (1979) Stoichiometric binding and regulation of insulin receptors on human diploid fibroblasts using physiologic insulin levels. J Biol Chem 254: 8762–8767
Gould R, Ginsberg B, Spector A (1982) Lipid effects on the binding properties of a reconstituted insulin receptor. J Biol Chem 257: 477–484
Mature J, Hollenberg M (1978) Insulin receptor: interaction with non-receptor glycoprotein from liver cell membranes. Proc Natl Acad Sci (USA) 75: 3070–3074
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Livingston, J.N., Lerea, K.M., Bolinder, J. et al. Binding and molecular weight properties of the insulin receptor from omental and subcutaneous adipocytes in human obesity. Diabetologia 27, 447–453 (1984). https://doi.org/10.1007/BF00273909
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00273909