Diagnostic procedures for catheter malfunction in programmable implantable intraperitoneal insulin infusion devices

N-terminal chain extension of unprotected amino acid amides and peptides with dipeptide amides using Cathepsin C (dipeptidyl aminopeptidase I, EC 3.4.14.1)-mediated reverse proteolysis in water was studied. Taking Pro-X-NH2 as the acyl donor, the sensitivity of the kinetically controlled peptide, coupling to pH value, temperature, acetonitrile addition, and nucleophile type were investigated. Basic or hydrophobic amino acids as the alpha-amino-N-nucleophile proved to be much more prone to catalyzed bond formation than their neutral, hydrophilic, or negatively charged analogues. In a preparative run a pentapeptide was obtained with 83% yield by directed and regioselective coupling of ProTrpNH2 with LysLeuPheNH2 catalyzed by Cathepsin C in aqueous buffer.     

Glucose inhibits phenobarbital-induced delta-aminolevulinate synthase expression in normal but not in diabetic rat hepatocytes

In the present work, we demonstrate the presence of a glucose inhibitory effect on the phenobarbital-mediated induction of the delta-aminolevulinate synthase mRNA in normal rat hepatocytes, consistent with the results obtained with the delta-aminolevulinate synthase activity previously reported. This "glucose effect" can be prevented by adding cAMP, adenylate cyclase activators, or a phosphodiesterase inhibitor. Delta-Aminolevulinate synthase mRNA half-life is not modified in the presence of phenobarbital or glucose. When the same experiments are performed using diabetic cells, no glucose effect is observed, even when the endogenous cAMP content is lowered to normal levels. The results obtained in this study suggest that glucose decreases delta-aminolevulinate synthase biosynthesis by acting at a pretranslational step. Assuming that the glucose effect operates by a repression mechanism exerted by metabolites derived from or related to glucose, the present results may reflect a derangement in the formation of these metabolites as a result of the abnormal metabolism operating in the diabetic state.