A new type of inhalation aerosol, characterized by particles of small mass density and large size, permitted the highly efficient delivery of inhaled therapeutics into the systemic circulation. Particles with mass densities less than 0.4 gram per cubic centimeter and mean diameters exceeding 5 micrometers were inspired deep into the lungs and escaped the lungs' natural clearance mechanisms until the inhaled particles delivered their therapeutic payload. Inhalation of large porous insulin particles resulted in elevated systemic levels of insulin and suppressed systemic glucose levels for 96 hours, whereas small nonporous insulin particles had this effect for only 4 hours. High systemic bioavailability of testosterone was also achieved by inhalation delivery of porous particles with a mean diameter (20 micrometers) approximately 10 times that of conventional inhaled therapeutic particles.

Glucose utilization and lactate metabolism were studied in isolated rat lungs perfused with a Krebs-Henseleit bicarbonate buffer, pH 7.4, containing either [U-14C]lactate, [U-14C]glucose, or [U-14C]alanine. Glucose uptake showed an apparent Km of 4.7 mM and a Vmax of 107 mumol-g dry wt-1-h-1. Lactate production under these conditions showed a Vmax of 82.9 mumol-g dry wt-1-h-1. At high circulating lactate level (7 mM), the perfused lung showed an increased capacity to utilize [U-14C]lactate with preferential incorporation into lung lipids. At equal molar concentration (5 mM) [U-14C]lactate was preferentially incorporated over [U-14C]glucose. Addition of 5 mM lactate to the perfusion medium did not affect lactate production. Perfused lungs from fasted rats showed higher lactate production, with increased amounts of [U-14C]alanine converted to lactate by the perfused lung, indicating lactate can also be derived from noncarbohydrate sources. These data show that under aerobic conditions the perfused lung can produce and utilize lactate simultaneously, and lactate can serve as a potential substrate for lung lipids.

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