ABSTRACT
Insulin has emerged as an important neuropeptide. Central actions of insulin appear to oppose those in the periphery. Insulin is transported across the blood-brain barrier (BBB) by a saturable transport system. The permeability of the BBB to insulin is altered by various events, but no studies exist that have examined the permeability of the BBB to insulin during infection or inflammation, states which can induce peripheral insulin resistance. We looked at the effects of lipopolysaccharide (LPS), a bacterial endotoxin and a powerful cytokine releaser, on the permeability of the BBB to human insulin in CD-1 mice. Intraperitoneal injections of LPS significantly increased the uptake by the brain of 131I-insulin and disrupted the BBB to 125I-albumin. After subtraction of the brain/serum ratio for 125I-albumin, brain/serum ratios for insulin were increased: 10.38 +/- 0.70 microl/g (LPS) vs. 3.62 +/- 0.27 microl/g (no LPS), P<0.0001, showing that LPS increased the uptake of insulin independent of BBB disruption. This increase in insulin uptake was due to enhanced saturable transport. Pretreatment with indomethacin 10 min before LPS injections enhanced BBB disruption, but not insulin transport. Pretreatment with the nitric oxide (NO) synthase inhibitor aminoguanidine had no effect on insulin or albumin uptake, but pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) enhanced insulin transport, but not BBB disruption. We conclude that LPS increases the saturable transport of insulin across the BBB independent of disruption and prostaglandins with potentiation by NO inhibition. Such increased transport could potentiate the central effects of insulin and so contribute to the peripheral insulin resistance seen with infection and inflammation.
Subject(s)
Blood-Brain Barrier/drug effects , Hypoglycemic Agents/pharmacokinetics , Insulin/pharmacokinetics , Lipopolysaccharides/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Blood-Brain Barrier/physiology , Enzyme Inhibitors/pharmacology , Guanidines/pharmacology , Indomethacin/pharmacology , Iodine Radioisotopes , Male , Mice , Mice, Inbred Strains , NG-Nitroarginine Methyl Ester/pharmacologyABSTRACT
The method used to manufacture a Young's double pinhole interferometer is dis ussed. This interferometer is destined to be used in a surface profilometer using two wavelengths so that the zero order fringe can be determined. Hence stringent requirements are placed on the absolute length difference between the two output fibers of a single mode coupler. These requirements are discussed along with the manufacturing process. The interferometer is shown along with measurements showing a length difference on the order of 6microm.
