Mario Di Girolamo

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 peptides 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.

Evolutionary Changes in Adipose Tissue Physiology

It is now about 10 years since the intensive investigation of adipose tissue began. Until the 1930’s, this tissue was considered a metabolically inert depot of excess calories stored as triglyceride. During the next 3 decades, a series of key observations gradually kindled interest in the possibility of a more dynamic role of the adipose organ in the body’s metabolism: The capacity of pituitary extracts to cause an acute mobilization of adipose tissue lipid (Best and Campbell, 1936); demonstration of the rapid turnover of adipose lipid by Schoenheimer and Rittenberg (1936); the avid uptake of glucose, and incorporation of the hexose carbons into stored lipid, by adipose tissue slices incubated in vitro (Shapiro and Wertheimer, 1948;Hausberger et al, 1954); discovery in 1956 of the circulating free fatty acids (FFA), recognition that this plasma lipid is secreted into the blood by the fat cells, and demonstration that its plasma concentration fluctuates continuously in rapid response to changes in carbohydrate intake and utilization (Gordon and Cherkes, 1956; Dole, 1956; Laurell, 1956).

Comparative Studies on the Physiology of Adipose Tissue1 1Investigations conducted in the authors' laboratory which are discussed in this review were supported by research grants AM 06056, AM 10715 and HE 05741 from the USPHS, and U-1820 and U-1562 from the Health Research Council of New York City.

Publisher Summary This chapter presents comparative studies on the physiology of adipose tissue. The adipose tissues of the other species studied differ from that of the lean rat or mouse in these respects : (1) the form in which stored triglyceride fatty acids are mobilized, (2) the nature of the principal extracellular carbohydrate that is metabolized by the fat cell, (3) the capacity to convert glucose to glyceride fatty acids, (4) the responsiveness to the glucose-transport effect of insulin, (5) responsiveness to the antilipolytic action of insulin, and (6) responsiveness to the various naturally occurring lipolytic agents. The notable species differences so far revealed by in vitro studies of adipose tissue are that insect adipose tissue differs from avian and mammalian adipose tissues by utilizing and releasing trehalose as the major extracellular carbohydrate, and by mobilizing stored triglyceride fatty acids principally as diglyceride. The adipose tissues of primate and carnivore orders of mammals are highly sensitive to catecholamines but have not yet been adequately studied in other respects. Interpretation of these comparative data is presently limited by the use of in vitro experimental design and heterologous peptide hormones in the majority of the investigations.