We evaluated the in vivo biological activity of in vitro extensively glycosylated insulin (GI) with the euglycemic-hyperinsulinemic glucose-clamp technique in postabsorptive nondiabetic subjects. Insulin-mediated glucose disposal was ∼30% lower (P < .03) with GI (9.2 ± 1.2 mg · kg−1 · min−1, mean ± SE) than with the nonglycosylated hormone (12.6 ± 0.7 mg · kg−1 · min−1) at comparable plasma insulin concentrations (∼90 μU/ml). Binding of GI to a specific receptor on circulating cells (erythrocytes and monocytes) was normal. We conclude that in vitro extensive glycosylation of insulin reduces its biological activity in vivo, as reflected by insulin-mediated glucose disposal, probably at a postreceptor level.

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