ORIGIN AND DISTRIBUTION OF THE HYPERGLYCEMIC-GLYCOGENOLYTIC FACTOR OF THE PANCREAS

Abstract

There are many references in the early literature (for a summary see Jensen (1)) to a transient hyperglycemia which is produced in man and animals on intravenous injection of various commercial insulin preparations.This hyperglycemia sets in a few minutes after injection, reaches a maximum in about 5 to 10 minutes, and is then overshadowed by the rapid fall of blood sugar to hypoglycemic levels.Biirger and Brandt (2), in particular, carried out an extensive investigation in order to determine the nature of this hyperglycemic factor.They were unable to separate it from insulin by isoelectric precipitation, alcohol fractionation, or adsorption and concluded that its chemical properties must be very similar to those of insulin.A separation was, however, effected by crystallizing insulin by the method of Abel et al. (3).As shown by several authors (l), this material did not cause an initial hyperglycemia, even on injection into the portal vein, It was then assumed that "impurities" were responsible for the hyperglycemic action of other insulin preparations and little attention was paid to this phenomenon.With the advent of new methods of crystallization, such as that of Scott and Fisher (4), it was apparently taken for granted that they would also lead to a separation of insulin from the hyperglycemic factor.That this is not the case was recently shown by de Duve, Hers, and Bouckaert (5) and confirmed by Olsen and Klein (6).These authors found that, with the exception of one insulin preparatioql all others, including crystalline zinc insulin, caused an initial hyperglycemia on intravenous injection in animals.Shipley and Hiimel (7) had demonstrated a glycogenolytic effect of insulin on liver slices in vitro, but it was shown by Sutherland and Cori (8) that this was not caused by insulin itself.The Danish insulin,l which failed to cause hyperglycemia in animals, was also without effect on liver