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Effects of the Long-Acting Insulin Analog Insulin Glargine on Cultured Human Skeletal Muscle Cells: Comparisons to Insulin and IGF-I

Veterans Affairs San Diego HealthCare System (9111G) and Department of Medicine, University of California-San Diego (T.P.C., L.C., S.M., R.R.H.), La Jolla, California 92093; and Aventis Pharm (G.S.), D-65926 Frankfurt, Germany

Address all correspondence and requests for reprints to: T. P. Ciaraldi, Ph.D., Department of Medicine (9111G), University of California-San Diego, La Jolla, California 92093. E-mail: tciaraldi{at}ucsd.edu

Abstract

The aim of this study was to determine whether the long-acting insulin analog, insulin glargine, behaves like human insulin for metabolic and mitogenic responses in differentiated cultured human skeletal muscle cells from nondiabetic and diabetic subjects. Human insulin and insulin glargine were equipotent in their ability to compete for [¹²⁵I]insulin binding. Insulin glargine displaced [¹²⁵I]IGF-I from the IGF-I-binding site with approximately 0.5% the potency of IGF-I. In nondiabetic muscle cells, all three ligands stimulated glucose uptake similarly, whereas the sensitivity of glucose uptake was greatest in response to IGF-I and lower and equal for human insulin and insulin glargine. In diabetic muscle cells, the final responsiveness of glucose uptake was greatest for IGF-I and equivalent for human insulin and insulin glargine; sensitivities were the same as those for nondiabetic cells. Thymidine uptake into DNA was stimulated foremost by IGF-I, whereas human insulin and insulin glargine showed equivalent, but greatly reduced, sensitivities and potencies (<1% IGF-I). Stimulation of Akt phosphorylation was slightly more responsive to IGF-I compared with human insulin and insulin glargine, with sensitivities similar to glucose uptake stimulation. We conclude that in human skeletal muscle cells, insulin glargine is equivalent to human insulin for metabolic responses and does not display augmented mitogenic effects.

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