Assessment of Glucagon-Like Peptide-1 Analogue and Renin Inhibitor on the Binding and Regulation of GLP-1 Receptor in Type 1 Diabetic Rat Hearts

This study focuses on the effects of long-term renin-angiotensin system suppression and/or incretin mimetic therapies on the regulation and binding affinity of GLP-1 to its receptor in the coronary endothelium (CE) and cardiomyocytes (CMs) of type 1 diabetic male Sprague-Dawley rats. The groups assessed are normal (N), streptozotocin-induced diabetic (D), Insulin treated (DI), Exendin-4 treated (DE), Aliskiren treated (DA), cotreated with Insulin and Aliskiren (DIA) and cotreated with exendin-4 and Aliskiren (DEA). Heart perfusion with 125I-GLP-1 was performed to estimate GLP-1 binding affinity (=1/−) to its receptor in the heart. Western Blotting was assessed to determine the expression variation of GLP-1 receptor in the heart. Plasma GLP-1 levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Diabetes decreased the value on CE and increased it on CMs compared to normal. The combination of Exendin-4 with Aliskiren showed a normalizing effect on the binding affinity of GLP-1 at the coronary endothelium, while at the cardiomyocyte level Exendin-4 treatment alone was the most effective

Interfacial barriers to the transport of sterols and other organic compounds at the aqueous polysorbate 80-hexadecane interface

1. 1. The interfacial barrier controlled transport of some biologically important solutes in the aqueous polysorbate 80-hexadecane system were investigated by means of the multiparticulate dispersion technique.2. 2. It was shown that the resistances to transport of cholesterol, [beta]-sitosterol, desmosterol, 20[alpha]-hydroxycholesterol, and vitamin D3 across the oil/water interface, were of the order of 103-107 times greater than those for diffusion controlled mechanisms.3. 3. The effects of changing the polysorbate-80 concentration upon the transport rates of the solutes were investigated. Cholesterol, [beta]-sitosterol, and desmosterol showed little or no change of their permeability coefficients in the 0.1-1% range of the surfactant concentration. These results suggest that for these compounds the drug-micelle complex is involved in the "transition" state. The data further suggest that a two-step mechanism is involved, viz. the approach of the solute loaded micelle to the interface and the unloading of the solute at the interface.4. 4. One of the interesting findings of this research relevant to biology is the possible correlation of these experiments to the intestinal absorption of cholesterol and [beta]-sitosterol. The present studies show that the interfacial resistance for [beta]-sitosterol is about 10 times greater than that for cholesterol, while rat intestinal absorption studies how that cholesterol is absorbed 5-10 times more rapidly than [beta]-sitosterol.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33647/1/0000156.pd