Prolonged hypoglycemic effect in diabetic dogs due to subcutaneous administration of insulin in liposomes
The biologic action of insulin entrapped in liposomes (phospholipid vesicles) has been investigated following subcutaneous injection to dogs made diabetic with a combination of alloxan and streptozotocin. The fate of the liposomally entrapped material was determined by injecting rats subcutaneously with either /sup 125/I-insulin or the labeled polysaccharide /sup 14/C-inulin, incorporated in liposomes labeled with /sup 3/H-cholesterol. Injection of liposome insulin (0.75 U/kg) to five diabetic dogs resulted in a mean (+/- SEM) blood glucose fall from 16.4 +/- 0.8 to 2.9 +/- 0.4 mmol/L. The glucose level had still not returned to baseline after 24 h and, correspondingly, immunoreactive insulin (IRI) could still be detected in frozen and thawed plasma 24 h after injection. In contrast, the hypoglycemic effect of the same dose of free insulin with or without empty liposomes virtually ended within 8 h and IRI levels returned to baseline by 3 h after injection. In experiments on rats with liposomally entrapped /sup 125/I-insulin or /sup 14/C-inulin the proportion of the injected dose of tracer recoverable by excision of the injection site remained constant after about 1 h and 70% of the dose was still fixed in subcutaneous tissue for at least 5 h thereafter. When the plasma collected 3 h after subcutaneous injection of labeled liposomes containing /sup 125/I-insulin was passed through a column of Sepharose 6B, 50-75% of the /sup 125/I-activity was found in the fractions associated with intact liposomes. One possibility for the persistence of the hypoglycemic effect and of measurable IRI following injection of liposome insulin could be the presence of intact liposomes in the circulation for many hours after adsorption had ceased.
- Research Organization:
- Laboratory for Endocrine Physiology and Pharmacology, National Institute for Medical Research, London, United Kingdom
- OSTI ID:
- 6187870
- Journal Information:
- Diabetes; (United States), Vol. 31:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DIABETES MELLITUS
BIOLOGICAL MODELS
GLUCOSE
METABOLISM
INSULIN
CARRIERS
SUBCUTANEOUS INJECTION
LIPOSOMES
USES
CARBON 14 COMPOUNDS
DOGS
INULIN
IODINE 125
PHYSIOLOGY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALDEHYDES
ANIMALS
BETA DECAY RADIOISOTOPES
CARBOHYDRATES
CELL CONSTITUENTS
DAYS LIVING RADIOISOTOPES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE DISEASES
HEXOSES
HORMONES
INJECTION
INTAKE
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
METABOLIC DISEASES
MONOSACCHARIDES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANOIDS
PEPTIDE HORMONES
POLYSACCHARIDES
RADIOISOTOPES
SACCHARIDES
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques
550501 - Metabolism- Tracer Techniques
550201 - Biochemistry- Tracer Techniques