Binding of Biosynthetic Human Insulin to Erythrocytes of Normal and Insulin-dependent Diabetic Subjects: Comparison with Pork and Human Pancreatic Insulin

Abstract

Biosynthetic human insulin (BHI) was compared with highly purified human pancreatic and pork insulin with regard to its ability to bind to erythrocytes of normal and insulin-dependent diabetic subjects (type I diabetes). The binding affinity or capacity of erythrocyte from both normal and diabetic subjects were comparable for biosynthetic and pancreatic human insulin. In contrast, binding of pork insulin to erythrocytes was significantly decreased at low insulin concentrations in normal as well as in diabetic subjects due to a reduced receptor affinity. The affinity of the "empty sites" was 5.25 x 10(-8) M-1 with pork insulin in normal subjects and 6.1 x 10(-8) M-1 in diabetic subjects; with both human insulins, the affinities were 6.9 x 10(-8) M-1 in normal subjects and 8.6 x 10(-8) M-1 in diabetic subjects. The number of insulin receptors per erythrocyte was calculated as being 30 in normal subjects and 35 in diabetic patients.

Insulin binding of human and porcine monocomponent insulin to monocytes in Type 1 (insulin-dependent) diabetic patients and control subjects

“…Furthermore, by comparing the binding of semi-synthetic human insulin and porcine insulin to isolated mononuclear leucocytes, identical binding properties in terms of receptor number and receptor affinity were found in both groups of diabetic and control subjects. These data are in contrast to recent findings by Bachman et al [4], who reported significant differences of insulin binding at lower insulin concentrations. Two factors should be taken into consideration with respect to the observed findings of Bachmann et al [4].…”

“…These data are in contrast to recent findings by Bachman et al [4], who reported significant differences of insulin binding at lower insulin concentrations. Two factors should be taken into consideration with respect to the observed findings of Bachmann et al [4]. Erythrocytes were used as targets in this study.…”

“…The observed different binding of porcine und human insulin in the study of Bachmann et al [4] could be due to the great difference in the specific radioactivity of the labelled insulins used.…”

“…Mutation of a single amino-acid in the insulin region thought to be involved in the binding of the receptor can cause marked impairment in binding to target tissues and subsequently in biological activity [3]. Bachmann et al [4] reported that at lower insulin concentrations, binding of biosynthetic human insulin and purified human pancreatic insulin was significantly higher than that of porcine insulin. Other comparative binding studies of human and porcine insulin in a variety of human and animal tissues [5] revealed identical binding behaviour regarding affinity, association and dissociation kinetics and negative cooperativity.…”

Human Insulin

“…Additionally, there were no significant differences between the insulins in their effect on the extent of glucose oxidation and incorporation by rat epididymal fat pads (Fussgaenger et al 1981), inhibition of isoprenaline (isoproterenol)-induced lipolysis and stimulation of lipogenesis in human adipocytes (Fussgaenger et al 1981;Khokher & Dandona 1982), and rat adipocytes (Khokher & Dandona 1982). Biosynthetic human in; sulin (Bachmann et al 1981) and semisynthetic human insulin (Vialettes et al 1982) exhibited the same binding affinity to human erythrocytes as pancreatic human and porcine insulins. Biosynthetic human in; sulin (Bachmann et al 1981) and semisynthetic human insulin (Vialettes et al 1982) exhibited the same binding affinity to human erythrocytes as pancreatic human and porcine insulins.…”