Determinants of Insulin Availability in Parenteral Nutrition Solutions

To study the route by which plasma insulin enters cerebrospinal fluid (CSF), the kinetics of uptake from plasma into cisternal CSF of both insulin and [14C]inulin were analyzed during intravenous infusion in anesthetized dogs. Four different mathematical models were used: three based on a two-compartment system (transport directly across the blood-CSF barrier by nonsaturable, saturable, or a combination of both mechanisms) and a fourth based on three compartments (uptake via an intermediate compartment). The kinetics of CSF uptake of [14C]inulin infused according to an "impulse" protocol were accurately accounted for only by the nonsaturable two-compartment model (determination coefficient [R2] = 0.879 +/- 0.044; mean +/- SEM; n = 5), consistent with uptake via diffusion across the blood-CSF barrier. When the same infusion protocol and model were used to analyze the kinetics of insulin uptake, the data fit (R2 = 0.671 +/- 0.037; n = 10) was significantly worse than that obtained with [14C]inulin (P = 0.02). Addition of a saturable component of uptake to the two-compartment model improved this fit, but was clearly inadequate for a subset of insulin infusion studies. In contrast, the three-compartment model accurately accounted for CSF insulin uptake in each study, regardless of infusion protocol (impulse infusion R2 = 0.947 +/- 0.026; n = 10; P less than 0.0001 vs. each two-compartment model; sustained infusion R2 = 0.981 +/- 0.003; n = 5). Thus, a model in which insulin passes through an intermediate compartment en route from plasma to CSF, as a part of a specialized transport system for the delivery of insulin to the brain, best accounts for the dynamics of this uptake process. This intermediate compartment could reside within the blood-CSF barrier or it may represent brain interstitial fluid, if CNS insulin uptake occurs preferentially across the blood-brain barrier.

Insulin is frequently required in total parenteral nutrition (TPN) solutions to control hyperglycemia. The purpose of this study was to evaluate the recovery of human insulin from standard TPN solutions with and without lipids and from TPN solutions with specialized amino acid formulations and to compare it to the insulin recovery from normal saline. All solutions were mixed in currently utilized PVC-free bags (ethylene vinyl acetate) and drained through PVC-containing tubing. Human insulin (Humulin-R) was spiked with 125I-labeled insulin and then added in concentrations of 10, 25, and 50 units to 1-liter bags containing 39-g amino acids (10% Freamine-III; or 6.9% Freamine HBC; or 8% Hepatamine), 257-g dextrose, electrolytes (Hyperlyte-R), 1000 units of heparin, MVI-12, and MTE-5 Concentrate. Alternate sets of bags contained 125 ml of 20% Intralipid and an appropriate amount of sterile water to keep the final volume at 1 liter. Actual clinical conditions of preparation, storage, and administration were simulated in this in vitro experiment. Multiple samples were collected during the 8-hr infusion period directly in gamma counter vials. All experiments and assays were done in triplicate. Our findings indicate that human insulin availability in TPN solutions is much higher (90%-95%) than the 50% suggested in the literature. Insulin recovery was not appreciably altered by adding lipids or by using Freamine HBC. Insulin recovery from TPN solutions was significantly reduced if they contained Hepatamine (87% and 88%, p less than 0.05) as compared to Freamine (90% and 94%).(ABSTRACT TRUNCATED AT 250 WORDS)