The Metabolic Effects of Pancreatic Hyperglycemic-Glycogenolytic Factor (Glucagon) ‡

The presence of hyperglycemia-producing properties in pancreatic extracts and commercial insulin preparations was noted as early as 1923.'9"N, However, FisherM believed the hyperglycemic activity resided in a "toxic fraction" which was also responsible for the local irritation and sterile abscesses associated with insulin therapy; and Collip's extracts'9 produced an unusually prolonged hyperglycemia of one to four days' duration. It is therefore uncertain whether the hyperglycemic effect of these early extracts was due to the specific hyperglycemic-glycogenolytic factor (HGF). In 1924, Kimball and Murline gave the name "glucagon" to the factor, but the earliest intensive investigators of its properties were the German workers, Burger and Kramer,'l who were dealing with the specific material and who demonstrated that the hyperglycemic effect was due to direct glycogenolytic effect on the liver. After the first successful crystallization of insulin by Abel et al.' in 1927, Geiling and de Lawder,'' and Burger and Kramer," demonstrated that crystalline insulin, even when injected intravenously, did not cause hyperglycemia. Glucagon was therefore considered merely an unimportant impurity, and during the next few years only Burger and his colleagues in Germany continued its study. These workers were the first to attempt its purification.8 In 1934 Scott'M succeeded in crystallizing insulin by a new, highly efficient method which was widely adopted by most commercial manufacturers. Insulin prepared by this method was found to have hyperglycemic and hepatic glycogenolytic properties.2" Lundsgaard et aL in 19397