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PubMed1994

Enhancement of intestinal insulin absorption by bile salt-fatty acid mixed micelles in dogs.

The pharmacokinetics and pharmacodynamics of porcine zinc insulin following intravenous (iv), intrajejunal, and ileocolonic delivery were evaluated in dogs. The concentration-time profile of plasma immunoreactive insulin following iv injection could be best described by a two-compartment model with a mean distribution half-life of 1.1 min and a mean elimination half-life of 5.6 min. Maximum hypoglycemia occurred at 15 min after injection. Intrajejunal administration of 10 units/kg insulin in phosphate-buffered saline resulted in minimal insulin absorption or hypoglycemia. Incorporation of mixed micelles containing 30 mM sodium glycocholate and 40 mM linoleic acid significantly improved enteral insulin absorption. When delivered with mixed micelles, the mean absolute bioavailability of insulin was 1.8%. To study the effect of intestinal site on insulin uptake, the same formulation was delivered to the ileocolonic region. The mean absolute bioavailability of insulin absorbed from this site was 0.6%. Delivery of insulin to both sites caused significant hypoglycemia in all dogs. Insulin combined with mixed micelles is enterally absorbed in dogs; however, the bioavailability is much lower than that observed in similar studies with rats.

Animals↗
PubMed1985

The differentiation of isomeric biological compounds using collision-induced dissociation of ions generated by fast atom bombardment.

Though fast atom bombardment ionization makes possible the ionization and molecular weight determination of polar or thermally labile biological compounds, the resulting mass spectra commonly give few or no fragment ions which would allow detailed structural analysis. In particular, isomeric compounds often give identical spectra. Collision-induced dissociation of ions resulting from fast atom bombardment ionization is shown to be a powerful combination which can differentiate isomeric substances. The technique is applied to isomeric bile acid salts and steroid conjugates and is capable of differentiating structural isomers which have similar fast atom bombardment mass spectra. A range of isomeric cyclic nucleotides is also shown to be amenable to the method. Sensitivity limits are examined and the unequivocal identification of two 3',5'-cyclic nucleotides isolated from living systems is demonstrated.

Animals↗
PubMed2006

Lipids isolated from bone induce the migration of human breast cancer cells.

Bone is the most common site to which breast cancer cells metastasize. We found that osteoblast-like MG63 cells and human bone tissue contain the bile acid salt sodium deoxycholate (DC). MG63 cells take up and accumulate DC from the medium, suggesting that the bone-derived DC originates from serum. DC released from MG63 cells or bone tissue promotes cell survival and induces the migration of metastatic human breast cancer MDA-MB-231 cells. The bile acid receptor farnesoid X receptor (FXR) antagonist Z-guggulsterone prevents the migration of these cells and induces apoptosis. DC increases the gene expression of FXR and induces its translocation to the nucleus of MDA-MB-231 cells. Nuclear translocation of FXR is concurrent with the increase of urokinase-type plasminogen activator (uPA) and the formation of F-actin, two factors critical for the migration of breast cancer cells. Our results suggest a novel mechanism by which DC-induced increase of uPA and binding to the uPA receptor of the same breast cancer cell self-propel its migration and metastasis to the bone.

Actins↗