Dietary Supplementation with Cholic Acid Reduces Insulin Secretion in Response to Intraperitoneal Glucose Administration in Rats.

The major characteristic of type 2 diabetes is insulin resistance, which is associated with plasma level of 12-hydroxylated bile acids (BAs) in humans. In this study, we investigated whether the rise of enterohepatic 12-hydroxylated BAs associates with glucose tolerance and/or insulin secretion using rats fed a diet supplemented with cholic acid (CA) at a level of 0.5 g/kg diet. Almost no increase was observed in plasma insulin in response to the intraperitoneal glucose administration in the CA-fed rats despite the significant increase of plasma insulin in control with the same treatment. In contrast, the changes in insulin secretion were observed in both groups and no difference was detected between the groups in the oral glucose tolerance test. Increases were observed in pancreatic expressions of Ins1 and Ins2 although the insulin protein content decreased in the pancreas without any sign in ectopic fat accumulation and histological damage in the CA-fed rats. Our results suggest that enterohepatic 12-hydroxylated BAs modulate insulin secretion in response to intraperitoneal glucose administration. The decrease in insulin store might be responsible for the reduction in the insulin secretion in the CA-fed rats.

Targeted delivery of chemotherapeutic agents using improved radiosensitive liquid core microcapsules and assessment of their antitumor effect.

PURPOSE: Radiation-sensitive microcapsules composed of alginate and hyaluronic acid are being developed. We report the development of improved microcapsules that were prepared using calcium- and yttrium-induced polymerization. We previously reported on the combined antitumor effect of carboplatin-containing microcapsules and radiotherapy. METHODS AND MATERIALS: We mixed a 0.1% (wt/vol) solution of hyaluronic acid with a 0.2% alginate solution. Carboplatin (l mg) and indocyanine green (12.5 microg) were added to this mixture, and the resultant material was used for capsule preparation. The capsules were prepared by spraying the material into a mixture containing a 4.34% CaCl(2) solution supplemented with 0-0.01% yttrium. These capsules were irradiated with single doses of 0.5, 1.0, 1.5, or 2 Gy (60)Co gamma-rays. Immediately after irradiation, the frequency of microcapsule decomposition was determined using a microparticle-induced X-ray emission camera. The amount of core content released was estimated by particle-induced X-ray emission and colorimetric analysis with 0.25% indocyanine green. The antitumor effect of the combined therapy was determined by monitoring its effects on the diameter of an inoculated Meth A fibrosarcoma. RESULTS: Microcapsules that had been polymerized using a 4.34% CaCl(2) solution supplemented with 5.0 x 10(-3)% (10(-3)% meant or 10%(-3)) yttrium exhibited the maximal decomposition, and the optimal release of core content occurred after 2-Gy irradiation. The microcapsules exhibited a synergistic antitumor effect combined with 2-Gy irradiation and were associated with reduced adverse effects. CONCLUSION: The results of our study have shown that our liquid core microcapsules can be used in radiotherapy for targeted delivery of chemotherapeutic agents.