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Abstract

Several carrier systems and targeting agents have been considered as means of delivering enzymes and drugs to specific tissues or cells. In this report insulin is shown to be effective in delivering enzyme-albumin conjugates to cells and tissues rich in insulin receptors. The complex is transported into cells by a process that resembles receptor-mediated endocytosis and can be identified in a lysosomal fraction. The enzyme-albumin-insulin complex retains its enzymatic activity and its ability to bind antibodies to insulin. It also has a hypoglycemic effect; however, plasma glucose concentrations can be maintained by glucose administration.

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References

BRADY, R.O., INVESTIGATIONS IN ENZYME REPLACEMENT THERAPY IN LIPID STORAGE DISEASES, FEDERATION PROCEEDINGS 34: 1310 (1975).
BRADY, R.O., METABOLIC CONTROL DI: CH9 (1980).
CUATRECASAS, P, RECENT PROGRESS IN HORMONE RESEARCH 31: 37 (1975).
DESNICK, R.J., TOWARD ENZYME THERAPY FOR LYSOSOMAL STORAGE DISEASES, PHYSIOLOGICAL REVIEWS 56: 57 (1976).
GAVIN, J.R., INSULIN-DEPENDENT REGULATION OF INSULIN RECEPTOR CONCENTRATIONS - DIRECT DEMONSTRATION IN CELL-CULTURE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 71: 84 (1974).
GONZALEZNORIEGA, A, CHLOROQUINE INHIBITS LYSOSOMAL-ENZYME PINOCYTOSIS AND ENHANCES LYSOSOMAL ENZYME-SECRETION BY IMPAIRING RECEPTOR RECYCLING, JOURNAL OF CELL BIOLOGY 85: 839 (1980).
GORDEN, P, INTERNALIZATION OF POLYPEPTIDE HORMONES - MECHANISM, INTRACELLULAR-LOCALIZATION AND SIGNIFICANCE, DIABETOLOGIA 18: 263 (1980).
GRABOWSKI, G.A., ENZYMES DRUGS: 167 (1981).
HUG, G, LYSOSOMES IN TYPE 2 GLYCOGENOSIS, JOURNAL OF CELL BIOLOGY 35: C1 (1967).
HUG, G, PHARMACOL REV 30: 565 (1979).
PAGANO, R.E., INTERACTIONS OF LIPOSOMES WITH MAMMALIAN-CELLS, ANNUAL REVIEW OF BIOPHYSICS AND BIOENGINEERING 7: 435 (1978).
PERTOFT, H, HETEROGENEITY OF LYSOSOMES ORIGINATING FROM RAT-LIVER PARENCHYMAL-CELLS - METABOLIC RELATIONSHIP OF SUB-POPULATIONS SEPARATED BY DENSITY-GRADIENT CENTRIFUGATION, BIOCHEMICAL JOURNAL 174: 309 (1978).
PILCH, P.F., J CELL BIOL 93: 133 (1983).
POZNANSKY, M.J., ARCH ALLERGY APPL IM 64: 11 (1981).
POZNANSKY, M.J., ANTIBODY-MEDIATED TARGETING OF ALPHA-1,4-GLUCOSIDASE-ALBUMIN POLYMERS TO RAT HEPATOCYTES - A MODEL FOR ENZYME THERAPY, BIOCHEMICAL JOURNAL 196: 89 (1981).
POZNANSKY, M.J., ALPHA-1,4-GLUCOSIDASE-ALBUMIN POLYMERS - INVITRO PROPERTIES AND ADVANTAGES FOR ENZYME REPLACEMENT THERAPY, CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 58: 322 (1980).
POZNANSKY, M.J., ADVANTAGES IN THE USE OF L-ASPARAGINASE-ALBUMIN POLYMER AS AN ANTI-TUMOR AGENT, CANCER RESEARCH 42: 1020 (1982).
POZNANSKY, M.J., DRUG DELIVERY SYSTEM: 253 (1980).
REMY, M.H., IMMUNOGENICITY AND ANTIGENICITY OF SOLUBLE CROSS-LINKED ENZYME-ALBUMIN POLYMERS - ADVANTAGES FOR ENZYME THERAPY, LANCET 2: 68 (1978).
SCHLESSINGER, J, DIRECT VISUALIZATION OF BINDING, AGGREGATION, AND INTERNALIZATION OF INSULIN AND EPIDERMAL GROWTH-FACTOR ON LIVING FIBROBLASTIC CELLS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 75: 2659 (1978).
Tsukada, Y., Proceedings of the National Academy of Sciences of the United States of America 79: 7896 (1982).
WILCHEK, M, STRUCTURE OF A SOLUBLE SUPER-ACTIVE INSULIN IS REVEALED BY NATURE OF COMPLEX BETWEEN CYANOGEN-BROMIDE-ACTIVATED SEPHAROSE AND AMINES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 72: 1055 (1975).

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Published In

Science
Volume 223 | Issue 4642
23 March 1984

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Published in print: 23 March 1984

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Mark J. Poznansky
Departments of Physiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
Rajkumari Singh
Departments of Physiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
Bhagirath Singh
Departments of Physiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
George Fantus
Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Canada H3A 2T8

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