Effect of glyburide on in vivo recycling of the hepatic insulin receptor
Sulfonylureas affect insulin action at both receptor and post-receptor sites, but their exact mechanism is poorly understood. In these studies, a novel technique was used to examine the influence of glyburide on in vivo cycling of the hepatic insulin receptor. Rats were gavage-fed with 5 mg/kg per day of glyburide solubilized in 60 percent polyethylene glycol and 40 percent phosphate buffer. Control rats were fed polyethylene glycol and buffer alone. After seven days, each rat was anesthetized, the abdomen was surgically exposed, and the animal was given a saturating bolus of 30 micrograms of unlabeled insulin via the portal vein. At seven specified times from 10 seconds to 45 minutes later, a second portal vein injection of a mixture of 1.5 microCi (0.015 micrograms) SVI-labeled insulin and 15 microCi THOH (a highly diffusible internal reference marker) was administered; 18 seconds later (time for one circulation), the right lobe of the liver was removed, and SVI and TH values were counted. The liver uptake index and the turnover half-time were then calculated. Glyburide caused a doubling of the turnover half-time for the receptor. This suggests that sulfonylureas potentiate the action of insulin either by increasing the dwell time of insulin on its receptor or by affecting an intracellular event that delays the recycling of the insulin receptor back to the cell surface plasma membrane.
- OSTI ID:
- 6086113
- Journal Information:
- Am. J. Med.; (United States), Vol. 3B
- Country of Publication:
- United States
- Language:
- English
Similar Records
Alterations by glyburide of effects of BRL 34915 and P 1060 on contraction, 86Rb efflux and the maxi-K+ channel in rat portal vein
/sup 54/Mn absorption and excretion in rats fed soy protein and casein diets
Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDES
BIOLOGICAL EFFECTS
INSULIN
RECEPTORS
LIVER
RADIONUCLIDE KINETICS
EXTRACELLULAR SPACE
IN VIVO
IODINE 125
RATS
TRITIUM COMPOUNDS
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PEPTIDE HORMONES
RADIOISOTOPES
RODENTS
SPACE
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
560172 - Radiation Effects- Nuclide Kinetics & Toxicology- Animals- (-1987)