Inactivation of Insulin by Adipose Tissue

A previous investigation in this laboratory demonstrated that rat adipose tissue contains an insoluble peptidase system which cleaves and inactivates adipokinetic hypophyseal peptides; adipose tissues from the rabbit and guinea pig possess little or no capacity to inactivate these peptides. The present study demonstrates that adipose tissues from the rat or hamster, but not from the rabbit or guinea pig, cleave and inactivate insulin. Incubation of bovine insulin with homogenized adipose tissue from the rat causes cleavage of the peptide into at least seven fragments and disappearance of the peptide's hypoglycemic activity. Unlike native insulin, the insulin fragments which contain tyrosine are soluble in 5 per cent trichloracetic acid. The insulin-inactivating system is located in the insoluble portion of homogenized adipose tissue. Inactivation of insulin does not proceed at a detectable rate at 0° C. The capacity of the insoluble fraction of rat adipose tissue homogenate to cleave and inactivate insulin is abolished by exposure to 100° C. for two minutes. An insulin-inactivating system with the same properties is found in lesser amount in hamster adipose tissue. It is not present in detectable amount in the adipose tissue of the rabbit or guinea pig. The adipose enzyme system which inactivates insulin resembles the system which inactivates hypophyseal peptides in regard to the characteristics described above.