Context. The insulin analog Lys^B3, Glu^B29 insulin (glulisine) displays accelerated in vivo bioavailability compared with native insulin.

Objective. Biological properties of this rapid-acting insulin analog were compared with actions of native insulin and IGF-1.

Design. Effects of the hormones on hormone binding, glucose uptake and thymidine uptake were evaluated in cultured human skeletal muscle cells.

Setting. Veterans Administration hospital for patient characterization and tissue biopsies, in vitro studies performed in research laboratory.

Patients or Other Participants. Skeletal muscle tissue was obtained from non-diabetic (n = 13) and type 2 diabetic (n = 14) subjects.

Intervention(s). Cultured skeletal muscle cells treated acutely (15-90 min) or chronically (16 h) with varying concentrations of hormones.

Main Outcome. Measures of sensitivity (EB₅₀ or EC₅₀) and potency (maximal response) for hormone binding and biological responses.

Results. Insulin and glulisine were comparable in their ability to displace insulin binding. Neither insulin nor glulisine competed efficiently for IGF-1 binding. Insulin, glulisine and IGF-1 were equipotent for stimulation of glucose uptake. Maximal stimulation of phosphorylation of Akt was greatest for IGF-1, while sensitivities were similar to those for glucose uptake. Sensitivities were comparable in muscle cells from non-diabetic and type 2 diabetic subjects. Stimulation of ³H-thymidine uptake was most responsive to IGF-1; insulin and glulisine were equally less effective with sensitivities 1-2% of that for IGF-1. Stimulation of p42/44 MAPK phosphorylation reflected the behavior of thymidine uptake.

Conclusions. While altered pharmacokinetics of glulisine can have therapeutic advantages, at the level of skeletal muscle glulisine is indistinguishable from native insulin.