Biologic activity and pharmacokinetics of biosynthetic human insulin in the rat

The biologic potency (plasma glucose depression) of pancreatic human insulin was compared with that of biosynthetic human insulin (BHI), manufactured by recombinant DNA techniques in bacteria, following intravenous injection in rats. The specific activity of the pancreatic human insulin was 32 U/mg, while that for BHI was 27 U/mg. These values were not significantly difference, but were higher than the value for pancreatic pork insulin (25 U/mg). The pharmacokinetics of i.v. injected A14-mono-125I-insulin (pork) were found to be similar to those observed for semisynthetic [3H]insulin (pork), the respective metabolic clearance rates (MCR) being 20.8 +/- 0.8 ml/min/kg (N = 4) and 23.6 +/- 1 ml/min/kg (N = 5) (P greater than 0.1). The MCR for A14-mono-125I-BHI was 24.6 +/- 2.2 ml/min/kg (N = 4), which was significantly higher (P less than 0.025) than the value for A14-mono-125I-pork insulin. BHI is thus no less active than pork insulin in rats and possibly somewhat more active. The small difference in activity may be due to increased affinity for rat insulin receptors, resulting in a more rapid MCR for BHI. In addition, the A14-monoiodinated insulin tracer used in these studies is indistinguishable from semisynthetic [3H]insulin in terms of its rate of clearance, indicating that the insulin molecule has not suffered any iodination damage and is thus a valid tracer for metabolic and receptor studies.