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This paper presents a survey of the biological potencies of a variety of naturally-occurring and semi-synthetic insulin analogues and a study of the joint biological action of some of these materials with native insulin. Biological activity was tested on isolated rat fat cells using lipogenesis from glucose as the metabolic index. A brief comparison using inhibition of fat cell lipolysis was included. The results indicated: 1. Analogue potencies varied considerably (0.4-100% insulin activity). Values obtained were mainly confirmatory but included two further B1-modified materials and a tricarbamylated insulin. The results supported previous indications on the relative roles of the A1, B1, and B29 residues of insulin for hormone activity. 2. Analogue bioactivities, whether assessed by stimulation of lipogenesis or inhibition of lipolysis, were similar for the four materials tested in both systems. The response of fat cells with respect to both metabolic indices occurred over a comparable range of insulin concentrations, with half maximal effects at 30-35 pmol 1(-1) insulin. 3. The presence of modified insulins appeared to alter the biological action of native insulin in vitro. Small effects of both potentiation and antagonism were identified.

In vitro bioactivity of insulin analogues: Lipogenic and anti-lipolytic potency and their interaction with the effect of native insulin