Inhibitory effects of "bound" insulin on insulin uptake by isolated tissues.

Abstract

“Bound” insulin preparations obtained from pooled human sera inhibited the uptake of crystalline insulin by isolated rat muscle (hemidiaphragm) and epididymal adipose tissue. When crystalline insulin alone was incubated with isolated tissues, its concentration in the incubating medium declined gradually, as shown by immunoassay of samples obtained at various intervals during the incubation. Addition of “bound” insulin preparations into the incubation medium greatly reduced the rate of disappearance of the crystalline insulin, “bound” insulin inhibiting the uptake of insulin by the tissues. The inhibition of insulin uptake by muscle, caused by “bound” insulin, was accompanied by inhibition of the biologic activity of insulin on this tissue. Preincubation of the isolated tissues with “bound” insulin, with whole fasting human sera from maturity-onset diabetics, or with crystalline insulin, prior to the addition of crystalline insulin, also resulted in significant inhibition of insulin uptake by these tissues. Synalbumin preparations obtained from fasting human sera by acid-ethanol extraction, as described by Vallance-Owen and collaborators, also inhibited the uptake of crystalline insulin by isolated muscle and adipose tissue and the biologic activity of insulin on muscle. Like “bound” insulin, the synalbumin extracts were inactive on isolated muscle and unreactive with anti-insulin antisera but exerted insulin-like activity on isolated adipose tissue. Their action when injected intraperitoneally into intact rats was similar to that of “bound” and crystalline insulin on the muscle and the adipose tissue. It is suggested that the synalbumin preparations obtained from sera by acid-ethanol extraction may contain the bulk of the serum “bound” insulin which contributes, at least in part, to the insulin inhibitory properties of these preparations.